7-88220388-A-G

Variant names:

• chr7-88220388-A-G
• rs80128501
• NM_198901.2:c.7-1446T>C

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_198901.2(SRI):​c.7-1446T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.151 in 147,930 control chromosomes in the GnomAD database, including 1,895 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.15 (1895 hom., cov: 31)
• Consequence: SRI NM_198901.2 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.612
• Publications: 4 publications found

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

ACMG classification

Our verdict: Benign. The variant received -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BP6: Variant 7-88220388-A-G is Benign according to our data. Variant chr7-88220388-A-G is described in ClinVar as Benign. ClinVar VariationId is 1253279.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.198 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_198901.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SRI	NM_198901.2		c.7-1446T>C		intron	N/A	NP_944490.1	P30626-2
	SRI	NM_001256892.2		c.7-1446T>C		intron	N/A	NP_001243821.1	P30626-3
	SRI-AS1	NR_120517.1		n.574+1164A>G		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SRI	ENST00000394641.7	TSL:2	c.7-1446T>C		intron	N/A	ENSP00000378137.3	P30626-2
	SRI	ENST00000431660.5	TSL:2	c.7-1446T>C		intron	N/A	ENSP00000391148.1	P30626-3
	SRI	ENST00000490437.5	TSL:2	c.7-3197T>C		intron	N/A	ENSP00000418512.1	C9J0K6

Frequencies

GnomAD3 genomes AF: 0.151 AC: 22376 AN: 147834 Hom.: 1895 Cov.: 31

Gnomad AFR AF: 0.0859

Gnomad AMI AF: 0.361

Gnomad AMR AF: 0.151

Gnomad ASJ AF: 0.201

Gnomad EAS AF: 0.00338

Gnomad SAS AF: 0.0913

Gnomad FIN AF: 0.136

Gnomad MID AF: 0.165

Gnomad NFE AF: 0.201

Gnomad OTH AF: 0.187

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

GnomAD4 genome AF: 0.151 AC: 22373 AN: 147930 Hom.: 1895 Cov.: 31 AF XY: 0.146 AC XY: 10512 AN XY: 71946

African (AFR) AF: 0.0857 AC: 3416 AN: 39866

American (AMR) AF: 0.151 AC: 2241 AN: 14864

Ashkenazi Jewish (ASJ) AF: 0.201 AC: 693 AN: 3450

East Asian (EAS) AF: 0.00339 AC: 17 AN: 5016

South Asian (SAS) AF: 0.0918 AC: 434 AN: 4728

European-Finnish (FIN) AF: 0.136 AC: 1275 AN: 9390

Middle Eastern (MID) AF: 0.174 AC: 50 AN: 288

European-Non Finnish (NFE) AF: 0.201 AC: 13540 AN: 67362

Other (OTH) AF: 0.185 AC: 381 AN: 2064

Alfa AF: 0.177 Hom.: 837

Bravo AF: 0.148

Asia WGS AF: 0.0430 AC: 150 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.082
DANN	Benign	0.56
PhyloP100		-0.61
PromoterAI		0.068	Neutral
Mutation Taster		=100/0	polymorphism (auto)

Splicing

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

Other links and lift over

dbSNP: rs80128501; hg19: chr7-87849703;