Genetic Variant SRI:c.136-150A>C (chr7-88217341-T-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 NM_003130.4(SRI):c.136-150A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00956 in 686,824 control chromosomes in the GnomAD database, including 322 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.030 ( 243 hom., cov: 32)

Exomes 𝑓: 0.0036 ( 79 hom. )

Consequence

SRI
NM_003130.4 intron

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.291

Publications

0 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 links:

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

SRI-AS1 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=-0.69).

BP6

Variant 7-88217341-T-G is Benign according to our data. Variant chr7-88217341-T-G is described in ClinVar as Benign. ClinVar VariationId is 1277351.Status of the report is criteria_provided_single_submitter, 1 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.101 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.136-150A>C	intron	N/A	NP_003121.1	P30626-1
SRI	NM_001256891.2		c.136-150A>C	intron	N/A	NP_001243820.1
SRI	NM_198901.2		c.91-150A>C	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.136-150A>C	intron	N/A	ENSP00000265729.3	P30626-1
SRI	ENST00000486860.5	TSL:1	n.170-150A>C	intron	N/A
SRI	ENST00000879560.1		c.166-150A>C	intron	N/A	ENSP00000549619.1

Frequencies

GnomAD3 genomes

AF:

0.0302

AC:

4597

AN:

152178

Hom.:

242

Cov.:

show subpopulations

Gnomad AFR

AF:

0.104

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0151

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000382

Gnomad OTH

AF:

0.0211

GnomAD4 exome

AF:

0.00365

AC:

1950

AN:

534528

Hom.:

AF XY:

0.00290

AC XY:

824

AN XY:

283898

show subpopulations

African (AFR)

AF:

0.103

AC:

1437

AN:

13944

American (AMR)

AF:

0.00713

AC:

167

AN:

23436

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

15986

East Asian (EAS)

AF:

0.00

AC:

AN:

31712

South Asian (SAS)

AF:

0.000141

AC:

AN:

49518

European-Finnish (FIN)

AF:

0.00

AC:

AN:

32886

Middle Eastern (MID)

AF:

0.00412

AC:

AN:

2182

European-Non Finnish (NFE)

AF:

0.000215

AC:

AN:

335616

Other (OTH)

AF:

0.00882

AC:

258

AN:

29248

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

146

220

293

366

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

104

130

<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:

0.0303

AC:

4614

AN:

152296

Hom.:

243

Cov.:

AF XY:

0.0297

AC XY:

2211

AN XY:

74476

show subpopulations

African (AFR)

AF:

0.104

AC:

4314

AN:

41546

American (AMR)

AF:

0.0150

AC:

230

AN:

15302

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5190

South Asian (SAS)

AF:

0.00

AC:

AN:

4818

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10620

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.000382

AC:

AN:

68030

Other (OTH)

AF:

0.0208

AC:

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

211

422

632

843

1054

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

144

192

240

<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:

0.0255

Hom.:

Bravo

AF:

0.0347

Asia WGS

AF:

0.00347

AC:

AN:

3476

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

-0.69

CADD

Benign

(source)

DANN

Benign

0.85

PhyloP100

-0.29

Mutation Taster

=100/0

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

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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