7-88220264-C-T

Variant names:

• chr7-88220264-C-T
• rs43100
• NM_198901.2:c.7-1322G>A

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_198901.2(SRI):​c.7-1322G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.251 in 152,174 control chromosomes in the GnomAD database, including 5,773 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency: Genomes: 𝑓 0.25 (5773 hom., cov: 33)
• Consequence: SRI NM_198901.2 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.907

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]

ENSG00000228113 (HGNC:):

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

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BP6: Variant 7-88220264-C-T is Benign according to our data. Variant chr7-88220264-C-T is described in ClinVar as [Benign]. Clinvar id is 1271507.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.728 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SRI	NM_003130.4	c.-238G>A		upstream_gene_variant		ENST00000265729.7	NP_003121.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SRI	ENST00000265729.7	c.-238G>A		upstream_gene_variant		1	NM_003130.4	ENSP00000265729.3

Frequencies

GnomAD3 genomes AF: 0.251 AC: 38136 AN: 152058 Hom.: 5755 Cov.: 33

Gnomad AFR AF: 0.260

Gnomad AMI AF: 0.122

Gnomad AMR AF: 0.334

Gnomad ASJ AF: 0.226

Gnomad EAS AF: 0.747

Gnomad SAS AF: 0.430

Gnomad FIN AF: 0.209

Gnomad MID AF: 0.155

Gnomad NFE AF: 0.186

Gnomad OTH AF: 0.234

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.251 AC: 38202 AN: 152174 Hom.: 5773 Cov.: 33 AF XY: 0.260 AC XY: 19311 AN XY: 74406

Gnomad4 AFR AF: 0.261

Gnomad4 AMR AF: 0.334

Gnomad4 ASJ AF: 0.226

Gnomad4 EAS AF: 0.748

Gnomad4 SAS AF: 0.430

Gnomad4 FIN AF: 0.209

Gnomad4 NFE AF: 0.186

Gnomad4 OTH AF: 0.238

Alfa AF: 0.104 Hom.: 129

Bravo AF: 0.261

Asia WGS AF: 0.563 AC: 1955 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

May 15, 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	1.2
DANN	Benign	0.81

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs43100; hg19: chr7-87849579;