chr1-158657525-T-C

Variant names:

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_003126.4(SPTA1):c.2757A>G(p.Glu919Glu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0172 in 1,613,754 control chromosomes in the GnomAD database, including 3,734 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.088 ( 1946 hom., cov: 32)

Exomes 𝑓: 0.0098 ( 1788 hom. )

Consequence

SPTA1
NM_003126.4 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:7

Conservation

PhyloP100: 0.0820

Publications

3 publications found

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 Gene-Disease associations (from GenCC):

hereditary spherocytosis type 3
Inheritance: AR Classification: DEFINITIVE, STRONG Submitted by: Laboratory for Molecular Medicine, Labcorp Genetics (formerly Invitae), Ambry Genetics, PanelApp Australia
elliptocytosis 2
Inheritance: AD Classification: STRONG, MODERATE Submitted by: Ambry Genetics, Laboratory for Molecular Medicine, PanelApp Australia, Labcorp Genetics (formerly Invitae)
pyropoikilocytosis, hereditary
Inheritance: AR Classification: STRONG, MODERATE Submitted by: PanelApp Australia, Labcorp Genetics (formerly Invitae), Ambry Genetics
hereditary elliptocytosis
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
hereditary spherocytosis
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

SPTA1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.58).

BP6

Variant 1-158657525-T-C is Benign according to our data. Variant chr1-158657525-T-C is described in ClinVar as Benign. ClinVar VariationId is 258924.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=0.082 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.298 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_003126.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SPTA1	NM_003126.4	MANE Select	c.2757A>G	p.Glu919Glu	synonymous	Exon 19 of 52	NP_003117.2	P02549-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SPTA1	ENST00000643759.2	MANE Select	c.2757A>G	p.Glu919Glu	synonymous	Exon 19 of 52	ENSP00000495214.1	P02549-1
	SPTA1	ENST00000647256.1		n.357A>G		non_coding_transcript_exon	Exon 2 of 3

Frequencies

GnomAD3 genomes

AF:

0.0878

AC:

13333

AN:

151818

Hom.:

1941

Cov.:

show subpopulations

Gnomad AFR

AF:

0.303

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0346

Gnomad ASJ

AF:

0.0170

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00332

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.0158

Gnomad NFE

AF:

0.00127

Gnomad OTH

AF:

0.0636

GnomAD2 exomes

AF:

0.0234

AC:

5846

AN:

249510

AF XY:

0.0182

show subpopulations

Gnomad AFR exome

AF:

0.312

Gnomad AMR exome

AF:

0.0163

Gnomad ASJ exome

AF:

0.0168

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.000186

Gnomad NFE exome

AF:

0.00151

Gnomad OTH exome

AF:

0.0132

GnomAD4 exome

AF:

0.00980

AC:

14329

AN:

1461818

Hom.:

1788

Cov.:

AF XY:

0.00857

AC XY:

6230

AN XY:

727214

show subpopulations

African (AFR)

AF:

0.314

AC:

10518

AN:

33448

American (AMR)

AF:

0.0186

AC:

830

AN:

44716

Ashkenazi Jewish (ASJ)

AF:

0.0161

AC:

420

AN:

26136

East Asian (EAS)

AF:

0.0000252

AC:

AN:

39696

South Asian (SAS)

AF:

0.00107

AC:

AN:

86258

European-Finnish (FIN)

AF:

0.000187

AC:

AN:

53418

Middle Eastern (MID)

AF:

0.0380

AC:

219

AN:

5768

European-Non Finnish (NFE)

AF:

0.000776

AC:

863

AN:

1111986

Other (OTH)

AF:

0.0228

AC:

1376

AN:

60392

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.472

Heterozygous variant carriers

668

1336

2003

2671

3339

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

314

628

942

1256

1570

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0879

AC:

13357

AN:

151936

Hom.:

1946

Cov.:

AF XY:

0.0856

AC XY:

6358

AN XY:

74278

show subpopulations

African (AFR)

AF:

0.303

AC:

12532

AN:

41390

American (AMR)

AF:

0.0346

AC:

528

AN:

15282

Ashkenazi Jewish (ASJ)

AF:

0.0170

AC:

AN:

3462

East Asian (EAS)

AF:

0.00

AC:

AN:

5154

South Asian (SAS)

AF:

0.00311

AC:

AN:

4816

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10568

Middle Eastern (MID)

AF:

0.0136

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00127

AC:

AN:

67946

Other (OTH)

AF:

0.0630

AC:

133

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

474

948

1421

1895

2369

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

120

240

360

480

600

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0365

Hom.:

2286

Bravo

AF:

0.0992

Asia WGS

AF:

0.0200

AC:

AN:

3478

EpiCase

AF:

0.00147

EpiControl

AF:

0.00267

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (3)

Elliptocytosis 2 (1)

Hereditary spherocytosis type 3 (1)

not specified (1)

Pyropoikilocytosis, hereditary (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.58

CADD

Benign

2.9

(source)

DANN

Benign

0.62

PhyloP100

0.082

Mutation Taster

=99/1

polymorphism (auto)

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over