Genetic Variant SRI:c.206-23A>G (chr7-88210948-T-C) – ACMG Classification: Benign (-20 pts)

Variant summary

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

The NM_003130.4(SRI):c.206-23A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.41 in 1,603,348 control chromosomes in the GnomAD database, including 137,779 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.40 ( 12614 hom., cov: 32)

Exomes 𝑓: 0.41 ( 125165 hom. )

Consequence

SRI
NM_003130.4 intron

Scores

Clinical Significance

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

Conservation

PhyloP100: -1.16

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:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.86).

BP6

Variant 7-88210948-T-C is Benign according to our data. Variant chr7-88210948-T-C is described in ClinVar as [Benign]. Clinvar id is 1291047.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.421 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein	UniProt
SRI	NM_003130.4 link	c.206-23A>G	intron_variant	Intron 3 of 7	ENST00000265729.7	NP_003121.1	P30626-1B4DHQ6
SRI	NM_001256891.2 link	c.206-23A>G	intron_variant	Intron 3 of 6		NP_001243820.1	P30626
SRI	NM_198901.2 link	c.161-23A>G	intron_variant	Intron 3 of 7		NP_944490.1	P30626-2
SRI	NM_001256892.2 link	c.161-23A>G	intron_variant	Intron 3 of 6		NP_001243821.1	P30626-3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SRI	ENST00000265729.7 link	c.206-23A>G		intron_variant	Intron 3 of 7	1	NM_003130.4	ENSP00000265729.3		P30626-1

Frequencies

GnomAD3 genomes

AF:

0.404

AC:

61357

AN:

151950

Hom.:

12604

Cov.:

show subpopulations

Gnomad AFR

AF:

0.401

Gnomad AMI

AF:

0.471

Gnomad AMR

AF:

0.371

Gnomad ASJ

AF:

0.404

Gnomad EAS

AF:

0.180

Gnomad SAS

AF:

0.297

Gnomad FIN

AF:

0.478

Gnomad MID

AF:

0.443

Gnomad NFE

AF:

0.425

Gnomad OTH

AF:

0.401

GnomAD3 exomes

AF:

0.382

AC:

95299

AN:

249678

Hom.:

18924

AF XY:

0.380

AC XY:

51292

AN XY:

135070

show subpopulations

Gnomad AFR exome

AF:

0.398

Gnomad AMR exome

AF:

0.311

Gnomad ASJ exome

AF:

0.402

Gnomad EAS exome

AF:

0.182

Gnomad SAS exome

AF:

0.309

Gnomad FIN exome

AF:

0.485

Gnomad NFE exome

AF:

0.430

Gnomad OTH exome

AF:

0.414

GnomAD4 exome

AF:

0.410

AC:

595714

AN:

1451280

Hom.:

125165

Cov.:

AF XY:

0.408

AC XY:

294776

AN XY:

722476

show subpopulations

Gnomad4 AFR exome

AF:

0.406

Gnomad4 AMR exome

AF:

0.323

Gnomad4 ASJ exome

AF:

0.409

Gnomad4 EAS exome

AF:

0.196

Gnomad4 SAS exome

AF:

0.309

Gnomad4 FIN exome

AF:

0.484

Gnomad4 NFE exome

AF:

0.426

Gnomad4 OTH exome

AF:

0.405

GnomAD4 genome

AF:

0.404

AC:

61396

AN:

152068

Hom.:

12614

Cov.:

AF XY:

0.403

AC XY:

29993

AN XY:

74336

show subpopulations

Gnomad4 AFR

AF:

0.401

Gnomad4 AMR

AF:

0.371

Gnomad4 ASJ

AF:

0.404

Gnomad4 EAS

AF:

0.180

Gnomad4 SAS

AF:

0.296

Gnomad4 FIN

AF:

0.478

Gnomad4 NFE

AF:

0.425

Gnomad4 OTH

AF:

0.398

Alfa

AF:

0.424

Hom.:

14284

Bravo

AF:

0.397

Asia WGS

AF:

0.255

AC:

891

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

May 16, 2021

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.86

CADD

Benign

0.86

DANN

Benign

0.60

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