7-88210843-G-GA

Variant names:

• chr7-88210843-G-GA
• rs57591302
• NM_003130.4:c.249+38dupT

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_Moderate BA1

The NM_003130.4(SRI):​c.249+38dupT variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.176 in 1,590,902 control chromosomes in the GnomAD database, including 25,998 homozygotes. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.17 (2363 hom., cov: 29)
  • Exomes 𝑓: 0.18 (23635 hom.)
• Consequence: SRI NM_003130.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.115

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]

ACMG classification

Verdict is Benign. Variant got -10 ACMG points.

• BP6: Variant 7-88210843-G-GA is Benign according to our data. Variant chr7-88210843-G-GA is described in ClinVar as [Benign]. Clinvar id is 1225315.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.188 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SRI	NM_003130.4	c.249+38dupT		intron_variant	Intron 4 of 7	ENST00000265729.7	NP_003121.1
SRI	NM_001256891.2	c.249+38dupT		intron_variant	Intron 4 of 6		NP_001243820.1
SRI	NM_198901.2	c.204+38dupT		intron_variant	Intron 4 of 7		NP_944490.1
SRI	NM_001256892.2	c.204+38dupT		intron_variant	Intron 4 of 6		NP_001243821.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SRI	ENST00000265729.7	c.249+38dupT		intron_variant	Intron 4 of 7	1	NM_003130.4	ENSP00000265729.3

Frequencies

GnomAD3 genomes AF: 0.174 AC: 26378 AN: 151706 Hom.: 2366 Cov.: 29

Gnomad AFR AF: 0.180

Gnomad AMI AF: 0.265

Gnomad AMR AF: 0.153

Gnomad ASJ AF: 0.229

Gnomad EAS AF: 0.0123

Gnomad SAS AF: 0.155

Gnomad FIN AF: 0.123

Gnomad MID AF: 0.231

Gnomad NFE AF: 0.191

Gnomad OTH AF: 0.215

GnomAD3 exomes AF: 0.153 AC: 37249 AN: 243384 Hom.: 3289 AF XY: 0.159 AC XY: 21002 AN XY: 131898

Gnomad AFR exome AF: 0.176

Gnomad AMR exome AF: 0.100

Gnomad ASJ exome AF: 0.234

Gnomad EAS exome AF: 0.0108

Gnomad SAS exome AF: 0.159

Gnomad FIN exome AF: 0.127

Gnomad NFE exome AF: 0.185

Gnomad OTH exome AF: 0.170

GnomAD4 exome AF: 0.176 AC: 253078 AN: 1439078 Hom.: 23635 Cov.: 28 AF XY: 0.176 AC XY: 126346 AN XY: 716604

Gnomad4 AFR exome AF: 0.180

Gnomad4 AMR exome AF: 0.105

Gnomad4 ASJ exome AF: 0.229

Gnomad4 EAS exome AF: 0.0135

Gnomad4 SAS exome AF: 0.162

Gnomad4 FIN exome AF: 0.133

Gnomad4 NFE exome AF: 0.186

Gnomad4 OTH exome AF: 0.174

GnomAD4 genome AF: 0.174 AC: 26386 AN: 151824 Hom.: 2363 Cov.: 29 AF XY: 0.169 AC XY: 12573 AN XY: 74186

Gnomad4 AFR AF: 0.179

Gnomad4 AMR AF: 0.153

Gnomad4 ASJ AF: 0.229

Gnomad4 EAS AF: 0.0124

Gnomad4 SAS AF: 0.155

Gnomad4 FIN AF: 0.123

Gnomad4 NFE AF: 0.191

Gnomad4 OTH AF: 0.217

Alfa AF: 0.191 Hom.: 518

Bravo AF: 0.174

Asia WGS AF: 0.0910 AC: 315 AN: 3470

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

May 15, 2021

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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Computational scores

Source: dbNSFP v4.3

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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

Other links and lift over

dbSNP: rs57591302; hg19: chr7-87840158;