dbSNP rs43111: SRI-AS1:n.663-2556A>G (chr7-88227200-A-G) – ACMG Classification: Benign (-14 pts)

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBA1

The NR_120517.1(SRI-AS1):n.575-2556A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.564 in 151,980 control chromosomes in the GnomAD database, including 24,495 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.56 ( 24495 hom., cov: 31)

Consequence

SRI-AS1
NR_120517.1 intron

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.892

Publications

8 publications found

Variant links:

Genes affected

SRI-AS1 (HGNC:40564): (SRI antisense RNA 1)

SRI-AS1 links:

SRI (HGNC:11292): (sorcin) This gene encodes a calcium-binding protein with multiple E-F hand domains that relocates from the cytoplasm to the sarcoplasmic reticulum in response to elevated calcium levels. In addition to regulating intracellular calcium homeostasis it also modulates excitation-contraction coupling in the heart. Alternative splicing results in multiple transcript variants encoding distinct proteins. Multiple pseudogenes exist for this gene. [provided by RefSeq, Mar 2012]

SRI Gene-Disease associations (from GenCC):

hypertrophic cardiomyopathy
Inheritance: AD Classification: NO_KNOWN Submitted by: Ambry Genetics

SRI links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -14 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.82).

BP6

Variant 7-88227200-A-G is Benign according to our data. Variant chr7-88227200-A-G is described in ClinVar as Benign. ClinVar VariationId is 1281341.Status of the report is criteria_provided_single_submitter, 1 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.789 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NR_120517.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	HGVSc	Effect	Exon Rank	Protein	UniProt
SRI-AS1	NR_120517.1	n.575-2556A>G	intron	N/A
SRI	NM_198901.2	c.-286T>C	upstream_gene	N/A	NP_944490.1	P30626-2
SRI	NM_001256892.2	c.-286T>C	upstream_gene	N/A	NP_001243821.1	P30626-3

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank
SRI-AS1	ENST00000591739.2	TSL:5	n.663-2556A>G	intron	N/A
SRI-AS1	ENST00000594469.5	TSL:5	n.128+7714A>G	intron	N/A
SRI-AS1	ENST00000718156.1		n.227+7976A>G	intron	N/A

Frequencies

GnomAD3 genomes

AF:

0.564

AC:

85606

AN:

151862

Hom.:

24477

Cov.:

show subpopulations

Gnomad AFR

AF:

0.477

Gnomad AMI

AF:

0.624

Gnomad AMR

AF:

0.622

Gnomad ASJ

AF:

0.565

Gnomad EAS

AF:

0.811

Gnomad SAS

AF:

0.653

Gnomad FIN

AF:

0.526

Gnomad MID

AF:

0.497

Gnomad NFE

AF:

0.583

Gnomad OTH

AF:

0.565

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome

AF:

0.564

AC:

85670

AN:

151980

Hom.:

24495

Cov.:

AF XY:

0.563

AC XY:

41830

AN XY:

74276

show subpopulations

African (AFR)

AF:

0.477

AC:

19769

AN:

41416

American (AMR)

AF:

0.621

AC:

9497

AN:

15282

Ashkenazi Jewish (ASJ)

AF:

0.565

AC:

1961

AN:

3468

East Asian (EAS)

AF:

0.810

AC:

4190

AN:

5174

South Asian (SAS)

AF:

0.654

AC:

3147

AN:

4814

European-Finnish (FIN)

AF:

0.526

AC:

5547

AN:

10548

Middle Eastern (MID)

AF:

0.510

AC:

150

AN:

294

European-Non Finnish (NFE)

AF:

0.583

AC:

39653

AN:

67966

Other (OTH)

AF:

0.564

AC:

1187

AN:

2106

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

1919

3838

5756

7675

9594

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

746

1492

2238

2984

3730

<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:

0.579

Hom.:

100198

Bravo

AF:

0.568

Asia WGS

AF:

0.697

AC:

2421

AN:

3478

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.82

CADD

Benign

0.22

(source)

DANN

Benign

0.51

PhyloP100

-0.89

PromoterAI

-0.00070

Neutral

(source)

Splicing

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

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over