rs7477

Positions:

• chr17-16342702-A-C

Variant summary

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

The NM_181716.3(CENPV):​c.*115T>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.446 in 1,256,326 control chromosomes in the GnomAD database, including 135,929 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 0.37 (12736 hom., cov: 31)
  • Exomes 𝑓: 0.46 (123193 hom.)
• Consequence: CENPV NM_181716.3 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0480

Genes affected

CENPV (HGNC:29920): (centromere protein V) Predicted to enable carbon-sulfur lyase activity and metal ion binding activity. Involved in pericentric heterochromatin assembly; positive regulation of cytokinesis; and regulation of chromosome organization. Acts upstream of or within ameboidal-type cell migration. Located in several cellular components, including midbody; nucleus; and spindle midzone. [provided by Alliance of Genome Resources, Apr 2022]

PIGL (HGNC:8966): (phosphatidylinositol glycan anchor biosynthesis class L) This gene encodes an enzyme that catalyzes the second step of glycosylphosphatidylinositol (GPI) biosynthesis, which is the de-N-acetylation of N-acetylglucosaminylphosphatidylinositol (GlcNAc-PI). Study of a similar rat enzyme suggests that this protein localizes to the endoplasmic reticulum. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.501 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CENPV	NM_181716.3	c.*115T>G		3_prime_UTR_variant	5/5	ENST00000299736.5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CENPV	ENST00000299736.5	c.*115T>G		3_prime_UTR_variant	5/5	1	NM_181716.3	P1

Frequencies

GnomAD3 genomes AF: 0.375 AC: 56859 AN: 151802 Hom.: 12738 Cov.: 31

Gnomad AFR AF: 0.164

Gnomad AMI AF: 0.498

Gnomad AMR AF: 0.380

Gnomad ASJ AF: 0.553

Gnomad EAS AF: 0.00520

Gnomad SAS AF: 0.274

Gnomad FIN AF: 0.502

Gnomad MID AF: 0.506

Gnomad NFE AF: 0.505

Gnomad OTH AF: 0.398

GnomAD4 exome AF: 0.455 AC: 502847 AN: 1104406 Hom.: 123193 Cov.: 14 AF XY: 0.453 AC XY: 252664 AN XY: 557706

Gnomad4 AFR exome AF: 0.153

Gnomad4 AMR exome AF: 0.297

Gnomad4 ASJ exome AF: 0.542

Gnomad4 EAS exome AF: 0.00119

Gnomad4 SAS exome AF: 0.293

Gnomad4 FIN exome AF: 0.489

Gnomad4 NFE exome AF: 0.505

Gnomad4 OTH exome AF: 0.438

GnomAD4 genome AF: 0.374 AC: 56866 AN: 151920 Hom.: 12736 Cov.: 31 AF XY: 0.371 AC XY: 27523 AN XY: 74210

Gnomad4 AFR AF: 0.163

Gnomad4 AMR AF: 0.380

Gnomad4 ASJ AF: 0.553

Gnomad4 EAS AF: 0.00541

Gnomad4 SAS AF: 0.274

Gnomad4 FIN AF: 0.502

Gnomad4 NFE AF: 0.505

Gnomad4 OTH AF: 0.400

Alfa AF: 0.479 Hom.: 27058

Bravo AF: 0.355

Asia WGS AF: 0.144 AC: 500 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	4.0
DANN	Benign	0.50
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

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: rs7477; hg19: chr17-16246016; COSMIC: COSV55333333; COSMIC: COSV55333333;