Genetic Variant SRI:c.250-245A>G (chr7-88210375-T-C) – ACMG Classification: Benign (-20 pts)

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_003130.4(SRI):c.250-245A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.148 in 519,352 control chromosomes in the GnomAD database, including 6,426 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.14 ( 1632 hom., cov: 32)

Exomes 𝑓: 0.15 ( 4794 hom. )

Consequence

SRI
NM_003130.4 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -1.41

Publications

7 publications found

Variant links:

Genes affected

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 -20 ACMG points.

BP4

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

BP6

Variant 7-88210375-T-C is Benign according to our data. Variant chr7-88210375-T-C is described in ClinVar as Benign. ClinVar VariationId is 1286151.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.182 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_003130.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
SRI	NM_003130.4	MANE Select	c.250-245A>G	intron	N/A	NP_003121.1	P30626-1
SRI	NM_001256891.2		c.250-245A>G	intron	N/A	NP_001243820.1
SRI	NM_198901.2		c.205-245A>G	intron	N/A	NP_944490.1	P30626-2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
SRI	ENST00000265729.7	TSL:1 MANE Select	c.250-245A>G	intron	N/A	ENSP00000265729.3	P30626-1
SRI	ENST00000486860.5	TSL:1	n.284-245A>G	intron	N/A
SRI	ENST00000879560.1		c.280-245A>G	intron	N/A	ENSP00000549619.1

Frequencies

GnomAD3 genomes

AF:

0.137

AC:

20856

AN:

152130

Hom.:

1632

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0781

Gnomad AMI

AF:

0.265

Gnomad AMR

AF:

0.131

Gnomad ASJ

AF:

0.195

Gnomad EAS

AF:

0.00308

Gnomad SAS

AF:

0.0890

Gnomad FIN

AF:

0.122

Gnomad MID

AF:

0.174

Gnomad NFE

AF:

0.185

Gnomad OTH

AF:

0.169

GnomAD4 exome

AF:

0.152

AC:

55945

AN:

367104

Hom.:

4794

Cov.:

AF XY:

0.150

AC XY:

29756

AN XY:

198168

show subpopulations

African (AFR)

AF:

0.0784

AC:

824

AN:

10512

American (AMR)

AF:

0.109

AC:

1776

AN:

16368

Ashkenazi Jewish (ASJ)

AF:

0.198

AC:

2120

AN:

10718

East Asian (EAS)

AF:

0.00462

AC:

100

AN:

21654

South Asian (SAS)

AF:

0.100

AC:

4406

AN:

44006

European-Finnish (FIN)

AF:

0.133

AC:

2462

AN:

18508

Middle Eastern (MID)

AF:

0.169

AC:

257

AN:

1524

European-Non Finnish (NFE)

AF:

0.183

AC:

40818

AN:

223338

Other (OTH)

AF:

0.155

AC:

3182

AN:

20476

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.508

Heterozygous variant carriers

2593

5185

7778

10370

12963

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

184

368

552

736

920

<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:

0.137

AC:

20848

AN:

152248

Hom.:

1632

Cov.:

AF XY:

0.132

AC XY:

9844

AN XY:

74448

show subpopulations

African (AFR)

AF:

0.0778

AC:

3233

AN:

41564

American (AMR)

AF:

0.130

AC:

1994

AN:

15294

Ashkenazi Jewish (ASJ)

AF:

0.195

AC:

677

AN:

3470

East Asian (EAS)

AF:

0.00309

AC:

AN:

5186

South Asian (SAS)

AF:

0.0893

AC:

430

AN:

4816

European-Finnish (FIN)

AF:

0.122

AC:

1292

AN:

10608

Middle Eastern (MID)

AF:

0.184

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.185

AC:

12559

AN:

67994

Other (OTH)

AF:

0.166

AC:

351

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

901

1803

2704

3606

4507

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

242

484

726

968

1210

<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:

0.169

Hom.:

3829

Bravo

AF:

0.136

Asia WGS

AF:

0.0420

AC:

146

AN:

3478

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (2)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.93

CADD

Benign

0.052

(source)

DANN

Benign

0.22

PhyloP100

-1.4

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

Details are displayed if max score is > 0.2

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

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over