rs6885297

Positions:

• chr5-96613298-T-C
• chr5-96613298-T-G

Variant summary

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

The NR_130776.1(LOC101929710):​n.355-17669T>C 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 0.283 in 152,048 control chromosomes in the GnomAD database, including 7,582 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 0.28 (7582 hom., cov: 32)
• Consequence: LOC101929710 NR_130776.1 intron, non_coding_transcript
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.250

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=-0.93).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.49 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
LOC101929710	NR_130776.1	n.355-17669T>C		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
	ENST00000502645.2	n.355-17669T>C		intron_variant, non_coding_transcript_variant		5
CAST	ENST00000505143.5	c.61-62241T>C		intron_variant		3
	ENST00000513158.1	n.542-17669T>C		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes AF: 0.283 AC: 42992 AN: 151930 Hom.: 7550 Cov.: 32

Gnomad AFR AF: 0.496

Gnomad AMI AF: 0.150

Gnomad AMR AF: 0.296

Gnomad ASJ AF: 0.189

Gnomad EAS AF: 0.353

Gnomad SAS AF: 0.146

Gnomad FIN AF: 0.222

Gnomad MID AF: 0.161

Gnomad NFE AF: 0.173

Gnomad OTH AF: 0.238

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

GnomAD4 genome AF: 0.283 AC: 43073 AN: 152048 Hom.: 7582 Cov.: 32 AF XY: 0.283 AC XY: 21060 AN XY: 74346

Gnomad4 AFR AF: 0.496

Gnomad4 AMR AF: 0.296

Gnomad4 ASJ AF: 0.189

Gnomad4 EAS AF: 0.354

Gnomad4 SAS AF: 0.146

Gnomad4 FIN AF: 0.222

Gnomad4 NFE AF: 0.173

Gnomad4 OTH AF: 0.241

Alfa AF: 0.189 Hom.: 6312

Bravo AF: 0.300

Asia WGS AF: 0.281 AC: 979 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	1.9
DANN	Benign	0.64

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs6885297; hg19: chr5-95949002;