rs882820

Positions:

• chr16-4206004-G-A
• chr16-4206004-G-T

Variant summary

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

The NM_001098814.2(SRL):​c.62-1370C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.258 in 151,864 control chromosomes in the GnomAD database, including 5,724 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 0.26 (5724 hom., cov: 31)
• Consequence: SRL NM_001098814.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.661

Genes affected

SRL (HGNC:11295): (sarcalumenin) Predicted to enable GTP binding activity. Predicted to be involved in endocytosis and endosomal transport. Predicted to act upstream of or within response to muscle activity involved in regulation of muscle adaptation and store-operated calcium entry. Predicted to be located in sarcoplasmic reticulum lumen and sarcoplasmic reticulum membrane. Predicted to be active in intracellular membrane-bounded organelle. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.402 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SRL	NM_001098814.2	c.62-1370C>T		intron_variant		ENST00000399609.7	NP_001092284.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SRL	ENST00000399609.7	c.62-1370C>T		intron_variant		1	NM_001098814.2	ENSP00000382518	P1
SRL	ENST00000572111.1	c.1439+723C>T		intron_variant, NMD_transcript_variant		1		ENSP00000461179
SRL	ENST00000537996.1	c.-65-1370C>T		intron_variant		2		ENSP00000440350

Frequencies

GnomAD3 genomes AF: 0.258 AC: 39085 AN: 151746 Hom.: 5697 Cov.: 31

Gnomad AFR AF: 0.406

Gnomad AMI AF: 0.202

Gnomad AMR AF: 0.199

Gnomad ASJ AF: 0.213

Gnomad EAS AF: 0.144

Gnomad SAS AF: 0.137

Gnomad FIN AF: 0.236

Gnomad MID AF: 0.229

Gnomad NFE AF: 0.205

Gnomad OTH AF: 0.236

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

GnomAD4 genome AF: 0.258 AC: 39153 AN: 151864 Hom.: 5724 Cov.: 31 AF XY: 0.253 AC XY: 18752 AN XY: 74218

Gnomad4 AFR AF: 0.407

Gnomad4 AMR AF: 0.199

Gnomad4 ASJ AF: 0.213

Gnomad4 EAS AF: 0.144

Gnomad4 SAS AF: 0.136

Gnomad4 FIN AF: 0.236

Gnomad4 NFE AF: 0.205

Gnomad4 OTH AF: 0.232

Alfa AF: 0.200 Hom.: 4186

Bravo AF: 0.262

Asia WGS AF: 0.181 AC: 630 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	5.7
DANN	Benign	0.53

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: rs882820; hg19: chr16-4256005;