rs10410651

Positions:

• chr19-44657628-T-C
• chr19-44657628-T-G

Variant summary

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

The NM_006505.5(PVR):​c.843-134T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.319 in 788,402 control chromosomes in the GnomAD database, including 46,789 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 0.40 (15247 hom., cov: 32)
  • Exomes 𝑓: 0.30 (31542 hom.)
• Consequence: PVR NM_006505.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -3.33

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)

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.94).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.707 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PVR	NM_006505.5	c.843-134T>C		intron_variant		ENST00000425690.8	NP_006496.4
PVR	NM_001135768.3	c.843-134T>C		intron_variant			NP_001129240.1
PVR	NM_001135769.3	c.843-134T>C		intron_variant			NP_001129241.1
PVR	NM_001135770.4	c.843-134T>C		intron_variant			NP_001129242.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PVR	ENST00000425690.8	c.843-134T>C		intron_variant		1	NM_006505.5	ENSP00000402060	P2
CEACAM16-AS1	ENST00000662585.1	n.476-25009A>G		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes AF: 0.402 AC: 61026 AN: 151776 Hom.: 15216 Cov.: 32

Gnomad AFR AF: 0.713

Gnomad AMI AF: 0.162

Gnomad AMR AF: 0.301

Gnomad ASJ AF: 0.300

Gnomad EAS AF: 0.460

Gnomad SAS AF: 0.426

Gnomad FIN AF: 0.232

Gnomad MID AF: 0.263

Gnomad NFE AF: 0.266

Gnomad OTH AF: 0.366

GnomAD4 exome AF: 0.299 AC: 190539 AN: 636506 Hom.: 31542 AF XY: 0.303 AC XY: 99220 AN XY: 327610

Gnomad4 AFR exome AF: 0.713

Gnomad4 AMR exome AF: 0.260

Gnomad4 ASJ exome AF: 0.308

Gnomad4 EAS exome AF: 0.481

Gnomad4 SAS exome AF: 0.409

Gnomad4 FIN exome AF: 0.235

Gnomad4 NFE exome AF: 0.265

Gnomad4 OTH exome AF: 0.313

GnomAD4 genome AF: 0.402 AC: 61102 AN: 151896 Hom.: 15247 Cov.: 32 AF XY: 0.399 AC XY: 29624 AN XY: 74240

Gnomad4 AFR AF: 0.713

Gnomad4 AMR AF: 0.301

Gnomad4 ASJ AF: 0.300

Gnomad4 EAS AF: 0.461

Gnomad4 SAS AF: 0.423

Gnomad4 FIN AF: 0.232

Gnomad4 NFE AF: 0.266

Gnomad4 OTH AF: 0.363

Alfa AF: 0.243 Hom.: 1000

Bravo AF: 0.418

Asia WGS AF: 0.449 AC: 1563 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	0.41
DANN	Benign	0.30
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: rs10410651; hg19: chr19-45160896; COSMIC: COSV51824041; COSMIC: COSV51824041;