Genetic Variant NM_003130.4:c.136-5A>G (chr7-88217196-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.136-5A>G variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0109 in 1,611,402 control chromosomes in the GnomAD database, including 411 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.023 ( 86 hom., cov: 32)

Exomes 𝑓: 0.0096 ( 325 hom. )

Consequence

SRI
NM_003130.4 splice_region, intron

Scores

Splicing: ADA: 0.0001947

Clinical Significance

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

Conservation

PhyloP100: -1.21

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 made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.8).

BP6

Variant 7-88217196-T-C is Benign according to our data. Variant chr7-88217196-T-C is described in ClinVar as [Benign]. Clinvar id is 1234720.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.0572 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SRI	NM_003130.4 link	c.136-5A>G		splice_region_variant, intron_variant	Intron 2 of 7	ENST00000265729.7	NP_003121.1	P30626-1B4DHQ6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SRI	ENST00000265729.7 link	c.136-5A>G		splice_region_variant, intron_variant	Intron 2 of 7	1	NM_003130.4	ENSP00000265729.3		P30626-1

Frequencies

GnomAD3 genomes

AF:

0.0231

AC:

3514

AN:

152030

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0594

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0143

Gnomad ASJ

AF:

0.0294

Gnomad EAS

AF:

0.00924

Gnomad SAS

AF:

0.0598

Gnomad FIN

AF:

0.0000947

Gnomad MID

AF:

0.0443

Gnomad NFE

AF:

0.00468

Gnomad OTH

AF:

0.0306

GnomAD3 exomes

AF:

0.0166

AC:

4170

AN:

251186

Hom.:

117

AF XY:

0.0183

AC XY:

2491

AN XY:

135780

show subpopulations

Gnomad AFR exome

AF:

0.0578

Gnomad AMR exome

AF:

0.00880

Gnomad ASJ exome

AF:

0.0303

Gnomad EAS exome

AF:

0.00881

Gnomad SAS exome

AF:

0.0586

Gnomad FIN exome

AF:

0.000462

Gnomad NFE exome

AF:

0.00497

Gnomad OTH exome

AF:

0.0150

GnomAD4 exome

AF:

0.00964

AC:

14067

AN:

1459254

Hom.:

325

Cov.:

AF XY:

0.0112

AC XY:

8134

AN XY:

726008

show subpopulations

Gnomad4 AFR exome

AF:

0.0611

Gnomad4 AMR exome

AF:

0.00959

Gnomad4 ASJ exome

AF:

0.0290

Gnomad4 EAS exome

AF:

0.00852

Gnomad4 SAS exome

AF:

0.0606

Gnomad4 FIN exome

AF:

0.000468

Gnomad4 NFE exome

AF:

0.00374

Gnomad4 OTH exome

AF:

0.0152

GnomAD4 genome

AF:

0.0231

AC:

3518

AN:

152148

Hom.:

Cov.:

AF XY:

0.0233

AC XY:

1731

AN XY:

74412

show subpopulations

Gnomad4 AFR

AF:

0.0591

Gnomad4 AMR

AF:

0.0143

Gnomad4 ASJ

AF:

0.0294

Gnomad4 EAS

AF:

0.00926

Gnomad4 SAS

AF:

0.0599

Gnomad4 FIN

AF:

0.0000947

Gnomad4 NFE

AF:

0.00468

Gnomad4 OTH

AF:

0.0345

Alfa

AF:

0.0138

Hom.:

Bravo

AF:

0.0243

EpiCase

AF:

0.00698

EpiControl

AF:

0.00842

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 06, 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

-0.80

CADD

Benign

0.24

DANN

Benign

0.68

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.00019

dbscSNV1_RF

Benign

0.018

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