7-88220257-C-G

Variant names:

• chr7-88220257-C-G
• rs117443479
• NM_198901.2:c.7-1315G>C

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.7-1315G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0567 in 152,318 control chromosomes in the GnomAD database, including 325 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency: Genomes: 𝑓 0.057 (325 hom., cov: 33)
• Consequence: SRI NM_198901.2 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.427

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=-0.85).
• BP6: Variant 7-88220257-C-G is Benign according to our data. Variant chr7-88220257-C-G is described in ClinVar as [Benign]. Clinvar id is 1279695.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0777 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SRI	NM_003130.4	c.-231G>C		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.-231G>C		upstream_gene_variant		1	NM_003130.4	ENSP00000265729.3

Frequencies

GnomAD3 genomes AF: 0.0568 AC: 8646 AN: 152204 Hom.: 325 Cov.: 33

Gnomad AFR AF: 0.0186

Gnomad AMI AF: 0.0197

Gnomad AMR AF: 0.0693

Gnomad ASJ AF: 0.123

Gnomad EAS AF: 0.00212

Gnomad SAS AF: 0.0624

Gnomad FIN AF: 0.0428

Gnomad MID AF: 0.0981

Gnomad NFE AF: 0.0794

Gnomad OTH AF: 0.0821

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

GnomAD4 genome AF: 0.0567 AC: 8642 AN: 152318 Hom.: 325 Cov.: 33 AF XY: 0.0560 AC XY: 4169 AN XY: 74484

Gnomad4 AFR AF: 0.0185

Gnomad4 AMR AF: 0.0690

Gnomad4 ASJ AF: 0.123

Gnomad4 EAS AF: 0.00212

Gnomad4 SAS AF: 0.0627

Gnomad4 FIN AF: 0.0428

Gnomad4 NFE AF: 0.0794

Gnomad4 OTH AF: 0.0809

Alfa AF: 0.0737 Hom.: 53

Bravo AF: 0.0560

Asia WGS AF: 0.0280 AC: 98 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	-0.85
CADD	Benign	5.3
DANN	Benign	0.63

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs117443479; hg19: chr7-87849572;