chr19-44658298-T-A

Variant names:

• chr19-44658298-T-A
• rs203709
• NM_006505.5:c.991+388T>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_006505.5(PVR):​c.991+388T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.425 in 152,182 control chromosomes in the GnomAD database, including 17,785 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 0.42 (17785 hom., cov: 33)
• Consequence: PVR NM_006505.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.01
• Publications: 9 publications found

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

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.783 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PVR	NM_006505.5	c.991+388T>A		intron_variant	Intron 5 of 7	ENST00000425690.8	NP_006496.4
PVR	NM_001135770.4	c.991+388T>A		intron_variant	Intron 5 of 5		NP_001129242.2
PVR	NM_001135768.3	c.991+388T>A		intron_variant	Intron 5 of 7		NP_001129240.1
PVR	NM_001135769.3	c.991+388T>A		intron_variant	Intron 5 of 6		NP_001129241.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PVR	ENST00000425690.8	c.991+388T>A		intron_variant	Intron 5 of 7	1	NM_006505.5	ENSP00000402060.2

Frequencies

GnomAD3 genomes AF: 0.424 AC: 64543 AN: 152064 Hom.: 17739 Cov.: 33

Gnomad AFR AF: 0.790

Gnomad AMI AF: 0.161

Gnomad AMR AF: 0.307

Gnomad ASJ AF: 0.299

Gnomad EAS AF: 0.461

Gnomad SAS AF: 0.424

Gnomad FIN AF: 0.231

Gnomad MID AF: 0.269

Gnomad NFE AF: 0.267

Gnomad OTH AF: 0.383

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

GnomAD4 genome AF: 0.425 AC: 64636 AN: 152182 Hom.: 17785 Cov.: 33 AF XY: 0.420 AC XY: 31267 AN XY: 74400

African (AFR) AF: 0.790 AC: 32817 AN: 41520

American (AMR) AF: 0.307 AC: 4699 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.299 AC: 1039 AN: 3470

East Asian (EAS) AF: 0.462 AC: 2384 AN: 5164

South Asian (SAS) AF: 0.421 AC: 2035 AN: 4828

European-Finnish (FIN) AF: 0.231 AC: 2453 AN: 10598

Middle Eastern (MID) AF: 0.255 AC: 75 AN: 294

European-Non Finnish (NFE) AF: 0.267 AC: 18186 AN: 67998

Other (OTH) AF: 0.379 AC: 801 AN: 2114

Alfa AF: 0.367 Hom.: 1629

Bravo AF: 0.443

Asia WGS AF: 0.455 AC: 1585 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.24
DANN	Benign	0.74
PhyloP100		-1.0
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs203709; hg19: chr19-45161566;