chr1-158610969-G-A

Position:

chr1-158610969-G-A

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_003126.4(SPTA1):c.*295C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.528 in 309,906 control chromosomes in the GnomAD database, including 44,059 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.52 ( 21092 hom., cov: 31)

Exomes 𝑓: 0.53 ( 22967 hom. )

Consequence

SPTA1
NM_003126.4 3_prime_UTR

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:5

Conservation

PhyloP100: 0.104

Variant links:

Genes affected

OR10Z1 (HGNC:14996): (olfactory receptor family 10 subfamily Z member 1) Olfactory receptors interact with odorant molecules in the nose, to initiate a neuronal response that triggers the perception of a smell. The olfactory receptor proteins are members of a large family of G-protein-coupled receptors (GPCR) arising from single coding-exon genes. Olfactory receptors share a 7-transmembrane domain structure with many neurotransmitter and hormone receptors and are responsible for the recognition and G protein-mediated transduction of odorant signals. The olfactory receptor gene family is the largest in the genome. The nomenclature assigned to the olfactory receptor genes and proteins for this organism is independent of other organisms. [provided by RefSeq, Jul 2008]

OR10Z1 links:

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.93).

BP6

Variant 1-158610969-G-A is Benign according to our data. Variant chr1-158610969-G-A is described in ClinVar as [Benign]. Clinvar id is 292920.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.607 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
OR10Z1	NM_001004478.2 linkuse as main transcript	c.*3589G>A		3_prime_UTR_variant	2/2	ENST00000641002.1
SPTA1	NM_003126.4 linkuse as main transcript	c.*295C>T		3_prime_UTR_variant	52/52	ENST00000643759.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
OR10Z1	ENST00000641002.1 linkuse as main transcript	c.*3589G>A		3_prime_UTR_variant	2/2		NM_001004478.2	P1
SPTA1	ENST00000643759.2 linkuse as main transcript	c.*295C>T		3_prime_UTR_variant	52/52		NM_003126.4	P1	P02549-1

Frequencies

GnomAD3 genomes

AF:

0.522

AC:

79215

AN:

151738

Hom.:

21066

Cov.:

show subpopulations

Gnomad AFR

AF:

0.424

Gnomad AMI

AF:

0.556

Gnomad AMR

AF:

0.544

Gnomad ASJ

AF:

0.570

Gnomad EAS

AF:

0.624

Gnomad SAS

AF:

0.434

Gnomad FIN

AF:

0.639

Gnomad MID

AF:

0.604

Gnomad NFE

AF:

0.553

Gnomad OTH

AF:

0.537

GnomAD4 exome

AF:

0.533

AC:

84218

AN:

158050

Hom.:

22967

Cov.:

AF XY:

0.524

AC XY:

43938

AN XY:

83832

show subpopulations

Gnomad4 AFR exome

AF:

0.411

Gnomad4 AMR exome

AF:

0.529

Gnomad4 ASJ exome

AF:

0.568

Gnomad4 EAS exome

AF:

0.597

Gnomad4 SAS exome

AF:

0.420

Gnomad4 FIN exome

AF:

0.613

Gnomad4 NFE exome

AF:

0.548

Gnomad4 OTH exome

AF:

0.547

GnomAD4 genome

AF:

0.522

AC:

79290

AN:

151856

Hom.:

21092

Cov.:

AF XY:

0.528

AC XY:

39182

AN XY:

74182

show subpopulations

Gnomad4 AFR

AF:

0.424

Gnomad4 AMR

AF:

0.544

Gnomad4 ASJ

AF:

0.570

Gnomad4 EAS

AF:

0.625

Gnomad4 SAS

AF:

0.435

Gnomad4 FIN

AF:

0.639

Gnomad4 NFE

AF:

0.553

Gnomad4 OTH

AF:

0.542

Alfa

AF:

0.541

Hom.:

10432

Bravo

AF:

0.515

Asia WGS

AF:

0.558

AC:

1940

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Nov 12, 2018	- -

Elliptocytosis 2

Benign:1

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. -

Hereditary spherocytosis type 3

Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jan 13, 2018

Pyropoikilocytosis, hereditary

Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jan 13, 2018

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.93

CADD

Benign

4.0

DANN

Benign

0.52

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

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