chr7-88206154-G-A

Variant names:

• chr7-88206154-G-A
• rs1063964
• ENST00000265729:c.*324C>T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_003130.4(SRI):​c.*324C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.295 in 359,442 control chromosomes in the GnomAD database, including 18,099 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.33 (9305 hom., cov: 32)
  • Exomes 𝑓: 0.27 (8794 hom.)
• Consequence: SRI NM_003130.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.350

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.461 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SRI	NM_003130.4	c.*324C>T		3_prime_UTR_variant	Exon 8 of 8	ENST00000265729.7	NP_003121.1
SRI	NM_198901.2	c.*324C>T		3_prime_UTR_variant	Exon 8 of 8		NP_944490.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SRI	ENST00000265729	c.*324C>T		3_prime_UTR_variant	Exon 8 of 8	1	NM_003130.4	ENSP00000265729.3
SRI	ENST00000419179	c.*324C>T		3_prime_UTR_variant	Exon 8 of 8	2		ENSP00000397609.1
SRI	ENST00000472930.6	n.*132C>T		downstream_gene_variant		2

Frequencies

GnomAD3 genomes AF: 0.333 AC: 50474 AN: 151774 Hom.: 9296 Cov.: 32

Gnomad AFR AF: 0.467

Gnomad AMI AF: 0.387

Gnomad AMR AF: 0.225

Gnomad ASJ AF: 0.224

Gnomad EAS AF: 0.0638

Gnomad SAS AF: 0.0870

Gnomad FIN AF: 0.357

Gnomad MID AF: 0.272

Gnomad NFE AF: 0.316

Gnomad OTH AF: 0.283

GnomAD4 exome AF: 0.267 AC: 55490 AN: 207550 Hom.: 8794 Cov.: 0 AF XY: 0.251 AC XY: 27834 AN XY: 110692

Gnomad4 AFR exome AF: 0.473

Gnomad4 AMR exome AF: 0.184

Gnomad4 ASJ exome AF: 0.234

Gnomad4 EAS exome AF: 0.0663

Gnomad4 SAS exome AF: 0.0912

Gnomad4 FIN exome AF: 0.355

Gnomad4 NFE exome AF: 0.317

Gnomad4 OTH exome AF: 0.277

GnomAD4 genome AF: 0.333 AC: 50517 AN: 151892 Hom.: 9305 Cov.: 32 AF XY: 0.326 AC XY: 24179 AN XY: 74238

Gnomad4 AFR AF: 0.466

Gnomad4 AMR AF: 0.225

Gnomad4 ASJ AF: 0.224

Gnomad4 EAS AF: 0.0638

Gnomad4 SAS AF: 0.0869

Gnomad4 FIN AF: 0.357

Gnomad4 NFE AF: 0.316

Gnomad4 OTH AF: 0.281

Alfa AF: 0.308 Hom.: 10542

Bravo AF: 0.329

Asia WGS AF: 0.0980 AC: 344 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	1.8
DANN	Benign	0.47

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

Other links and lift over

dbSNP: rs1063964; hg19: chr7-87835469;