rs261212

chr5-96605661-C-T

Variant summary

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

The NR_130776.1(LOC101929710):n.355-25306C>T variant causes a intron, non coding transcript change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.544 in 151,884 control chromosomes in the GnomAD database, including 22,446 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 0.54 (22446 hom., cov: 33)
• Consequence: LOC101929710 NR_130776.1 intron, non_coding_transcript
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0380

Genes affected

(HGNC:):

CAST (HGNC:1515): (calpastatin) The protein encoded by this gene is an endogenous calpain (calcium-dependent cysteine protease) inhibitor. It consists of an N-terminal domain L and four repetitive calpain-inhibition domains (domains 1-4), and it is involved in the proteolysis of amyloid precursor protein. The calpain/calpastatin system is involved in numerous membrane fusion events, such as neural vesicle exocytosis and platelet and red-cell aggregation. The encoded protein is also thought to affect the expression levels of genes encoding structural or regulatory proteins. Alternatively spliced transcript variants encoding different isoforms have been described. [provided by RefSeq, Jun 2010]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.98).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.588 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
LOC101929710	NR_130776.1	n.355-25306C>T		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
	ENST00000502645.2	n.355-25306C>T		intron_variant, non_coding_transcript_variant		5
CAST	ENST00000505143.5	c.61-69878C>T		intron_variant		3
	ENST00000513158.1	n.541+20628C>T		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes AF: 0.543 AC: 82459 AN: 151766 Hom.: 22409 Cov.: 33

Gnomad AFR AF: 0.594

Gnomad AMI AF: 0.499

Gnomad AMR AF: 0.545

Gnomad ASJ AF: 0.487

Gnomad EAS AF: 0.418

Gnomad SAS AF: 0.435

Gnomad FIN AF: 0.601

Gnomad MID AF: 0.551

Gnomad NFE AF: 0.525

Gnomad OTH AF: 0.510

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

GnomAD4 genome AF: 0.544 AC: 82552 AN: 151884 Hom.: 22446 Cov.: 33 AF XY: 0.544 AC XY: 40436 AN XY: 74276

Gnomad4 AFR AF: 0.594

Gnomad4 AMR AF: 0.545

Gnomad4 ASJ AF: 0.487

Gnomad4 EAS AF: 0.420

Gnomad4 SAS AF: 0.436

Gnomad4 FIN AF: 0.601

Gnomad4 NFE AF: 0.525

Gnomad4 OTH AF: 0.513

Alfa AF: 0.521 Hom.: 34148

Bravo AF: 0.541

Asia WGS AF: 0.478 AC: 1662 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
Cadd	Benign	2.4
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: rs261212; hg19: chr5-95941365;