1-158612856-T-C

Position:

chr1-158612856-T-C

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_003126.4(SPTA1):c.7095A>G(p.Ala2365Ala) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.542 in 1,613,310 control chromosomes in the GnomAD database, including 238,993 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.52 ( 21074 hom., cov: 31)

Exomes 𝑓: 0.54 ( 217919 hom. )

Consequence

SPTA1
NM_003126.4 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:13

Conservation

PhyloP100: -1.73

Variant links:

Genes affected

SPTA1 (HGNC:11272): (spectrin alpha, erythrocytic 1) This gene encodes a member of a family of molecular scaffold proteins that link the plasma membrane to the actin cytoskeleton and functions in the determination of cell shape, arrangement of transmembrane proteins, and organization of organelles. The encoded protein is primarily composed of 22 spectrin repeats which are involved in dimer formation. It forms a component of the erythrocyte plasma membrane. Mutations in this gene result in a variety of hereditary red blood cell disorders, including elliptocytosis-2, pyropoikilocytosis, and spherocytosis, type 3. [provided by RefSeq, Aug 2017]

SPTA1 links:

SPTA1 (HGNC:):

SPTA1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.73).

BP6

Variant 1-158612856-T-C is Benign according to our data. Variant chr1-158612856-T-C is described in ClinVar as [Benign]. Clinvar id is 258958.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr1-158612856-T-C is described in Lovd as [Benign].

BP7

Synonymous conserved (PhyloP=-1.73 with no splicing effect.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.605 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SPTA1	NM_003126.4 linkuse as main transcript	c.7095A>G	p.Ala2365Ala	synonymous_variant	51/52	ENST00000643759.2	NP_003117.2	P02549-1
SPTA1	XM_011509916.3 linkuse as main transcript	c.7095A>G	p.Ala2365Ala	synonymous_variant	52/53		XP_011508218.1	P02549-1
SPTA1	XM_011509917.4 linkuse as main transcript	c.7077A>G	p.Ala2359Ala	synonymous_variant	50/51		XP_011508219.1
SPTA1	XM_047428883.1 linkuse as main transcript	c.6774A>G	p.Ala2258Ala	synonymous_variant	51/52		XP_047284839.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
SPTA1	ENST00000643759.2 linkuse as main transcript	c.7095A>G	p.Ala2365Ala	synonymous_variant	51/52		NM_003126.4	ENSP00000495214.1	P02549-1
SPTA1	ENST00000481212.5 linkuse as main transcript	n.536A>G		non_coding_transcript_exon_variant	3/3	3
SPTA1	ENST00000498708.1 linkuse as main transcript	n.527A>G		non_coding_transcript_exon_variant	5/5	3

Frequencies

GnomAD3 genomes

AF:

0.521

AC:

79168

AN:

151856

Hom.:

21048

Cov.:

show subpopulations

Gnomad AFR

AF:

0.423

Gnomad AMI

AF:

0.555

Gnomad AMR

AF:

0.544

Gnomad ASJ

AF:

0.570

Gnomad EAS

AF:

0.623

Gnomad SAS

AF:

0.432

Gnomad FIN

AF:

0.638

Gnomad MID

AF:

0.608

Gnomad NFE

AF:

0.553

Gnomad OTH

AF:

0.537

GnomAD3 exomes

AF:

0.542

AC:

134682

AN:

248610

Hom.:

37137

AF XY:

0.539

AC XY:

72693

AN XY:

134936

show subpopulations

Gnomad AFR exome

AF:

0.423

Gnomad AMR exome

AF:

0.544

Gnomad ASJ exome

AF:

0.580

Gnomad EAS exome

AF:

0.611

Gnomad SAS exome

AF:

0.430

Gnomad FIN exome

AF:

0.635

Gnomad NFE exome

AF:

0.555

Gnomad OTH exome

AF:

0.550

GnomAD4 exome

AF:

0.544

AC:

795007

AN:

1461336

Hom.:

217919

Cov.:

AF XY:

0.541

AC XY:

393337

AN XY:

726994

show subpopulations

Gnomad4 AFR exome

AF:

0.427

Gnomad4 AMR exome

AF:

0.545

Gnomad4 ASJ exome

AF:

0.578

Gnomad4 EAS exome

AF:

0.599

Gnomad4 SAS exome

AF:

0.430

Gnomad4 FIN exome

AF:

0.630

Gnomad4 NFE exome

AF:

0.549

Gnomad4 OTH exome

AF:

0.548

GnomAD4 genome

AF:

0.521

AC:

79243

AN:

151974

Hom.:

21074

Cov.:

AF XY:

0.527

AC XY:

39156

AN XY:

74272

show subpopulations

Gnomad4 AFR

AF:

0.423

Gnomad4 AMR

AF:

0.544

Gnomad4 ASJ

AF:

0.570

Gnomad4 EAS

AF:

0.623

Gnomad4 SAS

AF:

0.433

Gnomad4 FIN

AF:

0.638

Gnomad4 NFE

AF:

0.553

Gnomad4 OTH

AF:

0.542

Alfa

AF:

0.542

Hom.:

9931

Bravo

AF:

0.515

Asia WGS

AF:

0.559

AC:

1941

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:13

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:4

Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 29, 2024	- -
Benign, criteria provided, single submitter	clinical testing	ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories	Nov 30, 2023	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Nov 12, 2018	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

not specified

Benign:3

Benign, criteria provided, single submitter	clinical testing	PreventionGenetics, part of Exact Sciences	-	- -
Benign, no assertion criteria provided	clinical testing	Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen	-	- -
Benign, no assertion criteria provided	clinical testing	Genome Diagnostics Laboratory, University Medical Center Utrecht	-	- -

Elliptocytosis 2

Benign:2

Benign, criteria provided, single submitter	clinical testing	Illumina Laboratory Services, Illumina	Jan 13, 2018	This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -
Benign, criteria provided, single submitter	clinical testing	Genome-Nilou Lab	Jul 15, 2021	- -

Hereditary spherocytosis type 3

Benign:2

Benign, criteria provided, single submitter	clinical testing	Illumina Laboratory Services, Illumina	Jan 13, 2018	This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -
Benign, criteria provided, single submitter	clinical testing	Genome-Nilou Lab	Jul 15, 2021	- -

Pyropoikilocytosis, hereditary

Benign:2

Benign, criteria provided, single submitter	clinical testing	Genome-Nilou Lab	Jul 15, 2021	- -
Benign, criteria provided, single submitter	clinical testing	Illumina Laboratory Services, Illumina	Jan 13, 2018	This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.73

CADD

Benign

4.3

DANN

Benign

0.58

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over