rs714948

Positions:

• chr19-44662645-A-C

Variant summary

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

The NM_006505.5(PVR):​c.*834A>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.926 in 152,318 control chromosomes in the GnomAD database, including 65,482 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 0.93 (65427 hom., cov: 31)
  • Exomes 𝑓: 0.94 (55 hom.)
• Consequence: PVR NM_006505.5 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0640

Genes affected

PVR (HGNC:9705): (PVR cell adhesion molecule) The protein encoded by this gene is a transmembrane glycoprotein belonging to the immunoglobulin superfamily. The external domain mediates cell attachment to the extracellular matrix molecule vitronectin, while its intracellular domain interacts with the dynein light chain Tctex-1/DYNLT1. The gene is specific to the primate lineage, and serves as a cellular receptor for poliovirus in the first step of poliovirus replication. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Oct 2008]

CEACAM16-AS1 (HGNC:55317): (CEACAM16, CEACAM19 and PVR antisense RNA 1)

CEACAM19 (HGNC:31951): (CEA cell adhesion molecule 19) Predicted to be integral component of membrane. [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=-0.85).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.977 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PVR	NM_006505.5	c.*834A>C		3_prime_UTR_variant	8/8	ENST00000425690.8	NP_006496.4
PVR	NM_001135768.3	c.*834A>C		3_prime_UTR_variant	8/8		NP_001129240.1
PVR	NM_001135769.3	c.*834A>C		3_prime_UTR_variant	7/7		NP_001129241.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PVR	ENST00000425690.8	c.*834A>C		3_prime_UTR_variant	8/8	1	NM_006505.5	ENSP00000402060	P2
CEACAM16-AS1	ENST00000662585.1	n.476-30026T>G		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes AF: 0.926 AC: 140828 AN: 152074 Hom.: 65371 Cov.: 31

Gnomad AFR AF: 0.980

Gnomad AMI AF: 0.862

Gnomad AMR AF: 0.953

Gnomad ASJ AF: 0.942

Gnomad EAS AF: 1.00

Gnomad SAS AF: 0.978

Gnomad FIN AF: 0.861

Gnomad MID AF: 0.984

Gnomad NFE AF: 0.888

Gnomad OTH AF: 0.933

GnomAD4 exome AF: 0.937 AC: 118 AN: 126 Hom.: 55 Cov.: 0 AF XY: 0.947 AC XY: 89 AN XY: 94

Gnomad4 AFR exome AF: 1.00

Gnomad4 AMR exome AF: 1.00

Gnomad4 NFE exome AF: 0.929

Gnomad4 OTH exome AF: 1.00

GnomAD4 genome AF: 0.926 AC: 140942 AN: 152192 Hom.: 65427 Cov.: 31 AF XY: 0.927 AC XY: 68989 AN XY: 74398

Gnomad4 AFR AF: 0.980

Gnomad4 AMR AF: 0.953

Gnomad4 ASJ AF: 0.942

Gnomad4 EAS AF: 1.00

Gnomad4 SAS AF: 0.977

Gnomad4 FIN AF: 0.861

Gnomad4 NFE AF: 0.888

Gnomad4 OTH AF: 0.934

Alfa AF: 0.901 Hom.: 33790

Bravo AF: 0.936

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	1.1
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs714948; hg19: chr19-45165912;