5-96626887-C-T

Position:

• chr5-96626887-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.355-4080C>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 0.235 in 152,140 control chromosomes in the GnomAD database, including 5,174 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 0.24 (5174 hom., cov: 33)
• Consequence: LOC101929710 NR_130776.1 intron, non_coding_transcript
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.91

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=-0.96).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.437 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
LOC101929710	NR_130776.1	n.355-4080C>T		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
	ENST00000502645.2	n.355-4080C>T		intron_variant, non_coding_transcript_variant		5
CAST	ENST00000505143.5	c.61-48652C>T		intron_variant		3		ENSP00000422957
	ENST00000513158.1	n.542-4080C>T		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes AF: 0.236 AC: 35809 AN: 152022 Hom.: 5176 Cov.: 33

Gnomad AFR AF: 0.0702

Gnomad AMI AF: 0.178

Gnomad AMR AF: 0.281

Gnomad ASJ AF: 0.234

Gnomad EAS AF: 0.452

Gnomad SAS AF: 0.310

Gnomad FIN AF: 0.290

Gnomad MID AF: 0.364

Gnomad NFE AF: 0.296

Gnomad OTH AF: 0.245

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

GnomAD4 genome AF: 0.235 AC: 35813 AN: 152140 Hom.: 5174 Cov.: 33 AF XY: 0.239 AC XY: 17767 AN XY: 74372

Gnomad4 AFR AF: 0.0700

Gnomad4 AMR AF: 0.281

Gnomad4 ASJ AF: 0.234

Gnomad4 EAS AF: 0.452

Gnomad4 SAS AF: 0.310

Gnomad4 FIN AF: 0.290

Gnomad4 NFE AF: 0.296

Gnomad4 OTH AF: 0.247

Alfa AF: 0.288 Hom.: 8764

Bravo AF: 0.229

Asia WGS AF: 0.337 AC: 1170 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	0.63
DANN	Benign	0.66

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs10515241; hg19: chr5-95962591;