rs203710

Positions:

• chr19-44658770-G-A
• chr19-44658770-G-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BS1 BS2

The NM_006505.5(PVR):​c.1020G>A​(p.Met340Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.021 in 1,611,156 control chromosomes in the GnomAD database, including 435 homozygotes. In-silico tool predicts a benign outcome for this variant. 5/6 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.014 (26 hom., cov: 32)
  • Exomes 𝑓: 0.022 (409 hom.)
• Consequence: PVR NM_006505.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.99

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 (MetaRNN=0.003705889).
• BS1: Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.0138 (2102/152314) while in subpopulation NFE AF= 0.0244 (1659/68038). AF 95% confidence interval is 0.0234. There are 26 homozygotes in gnomad4. There are 930 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd4 at 26 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PVR	NM_006505.5	c.1020G>A	p.Met340Ile	missense_variant	6/8	ENST00000425690.8
PVR	NM_001135770.4	c.1020G>A	p.Met340Ile	missense_variant	6/6
PVR	NM_001135768.3	c.1015+5G>A		splice_donor_5th_base_variant, intron_variant
PVR	NM_001135769.3	c.991+860G>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PVR	ENST00000425690.8	c.1020G>A	p.Met340Ile	missense_variant	6/8	1	NM_006505.5	P2
CEACAM16-AS1	ENST00000662585.1	n.476-26151C>T		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes AF: 0.0138 AC: 2102 AN: 152196 Hom.: 26 Cov.: 32

Gnomad AFR AF: 0.00471

Gnomad AMI AF: 0.0241

Gnomad AMR AF: 0.00851

Gnomad ASJ AF: 0.000865

Gnomad EAS AF: 0.000192

Gnomad SAS AF: 0.00683

Gnomad FIN AF: 0.00367

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.0244

Gnomad OTH AF: 0.00909

GnomAD4 exome AF: 0.0217 AC: 31693 AN: 1458842 Hom.: 409 Cov.: 30 AF XY: 0.0213 AC XY: 15453 AN XY: 725976

Gnomad4 AFR exome AF: 0.00311

Gnomad4 AMR exome AF: 0.00568

Gnomad4 ASJ exome AF: 0.000613

Gnomad4 EAS exome AF: 0.000101

Gnomad4 SAS exome AF: 0.00700

Gnomad4 FIN exome AF: 0.00524

Gnomad4 NFE exome AF: 0.0264

Gnomad4 OTH exome AF: 0.0187

GnomAD4 genome AF: 0.0138 AC: 2102 AN: 152314 Hom.: 26 Cov.: 32 AF XY: 0.0125 AC XY: 930 AN XY: 74498

Gnomad4 AFR AF: 0.00469

Gnomad4 AMR AF: 0.00850

Gnomad4 ASJ AF: 0.000865

Gnomad4 EAS AF: 0.000193

Gnomad4 SAS AF: 0.00684

Gnomad4 FIN AF: 0.00367

Gnomad4 NFE AF: 0.0244

Gnomad4 OTH AF: 0.00900

Alfa AF: 0.0206 Hom.: 63

Bravo AF: 0.0139

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.15
BayesDel_noAF	Benign	-0.97
CADD	Benign	0.019
DEOGEN2	Benign	0.0077	T;T
LIST_S2	Benign	0.35	T;T
MetaRNN	Benign	0.0037	T;T
Sift4G	Benign	0.48	T;T
Vest4		0.048
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0
gMVP		0.11

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs203710; hg19: chr19-45162038;