7-100221304-C-T

Position:

• chr7-100221304-C-T

Variant summary

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

The NM_001397246.1(PVRIG):​c.*53C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.506 in 1,381,220 control chromosomes in the GnomAD database, including 178,399 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 0.50 (19418 hom., cov: 33)
  • Exomes 𝑓: 0.51 (158981 hom.)
• Consequence: PVRIG NM_001397246.1 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0540

Genes affected

PVRIG (HGNC:32190): (PVR related immunoglobulin domain containing) Enables phosphatase binding activity and signaling receptor activity. Involved in negative regulation of T cell receptor signaling pathway. Located in plasma membrane. [provided by Alliance of Genome Resources, Apr 2022]

CASTOR3P (HGNC:29954): (CASTOR family member 3, pseudogene) Predicted to be involved in cellular response to L-arginine and negative regulation of TORC1 signaling. Predicted to be active in cytosol. [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=-0.83).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.556 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PVRIG	NM_001397246.1	c.*53C>T		3_prime_UTR_variant	5/5	ENST00000699088.1
CASTOR3P	NR_028040.1	n.913+1293G>A		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PVRIG	ENST00000699088.1	c.*53C>T		3_prime_UTR_variant	5/5		NM_001397246.1	A2
CASTOR3P	ENST00000649671.1	n.775+2266G>A		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes AF: 0.502 AC: 76314 AN: 151962 Hom.: 19415 Cov.: 33

Gnomad AFR AF: 0.544

Gnomad AMI AF: 0.424

Gnomad AMR AF: 0.402

Gnomad ASJ AF: 0.452

Gnomad EAS AF: 0.312

Gnomad SAS AF: 0.576

Gnomad FIN AF: 0.488

Gnomad MID AF: 0.535

Gnomad NFE AF: 0.514

Gnomad OTH AF: 0.507

GnomAD4 exome AF: 0.506 AC: 621884 AN: 1229140 Hom.: 158981 Cov.: 18 AF XY: 0.507 AC XY: 305132 AN XY: 601264

Gnomad4 AFR exome AF: 0.549

Gnomad4 AMR exome AF: 0.352

Gnomad4 ASJ exome AF: 0.461

Gnomad4 EAS exome AF: 0.335

Gnomad4 SAS exome AF: 0.580

Gnomad4 FIN exome AF: 0.504

Gnomad4 NFE exome AF: 0.511

Gnomad4 OTH exome AF: 0.500

GnomAD4 genome AF: 0.502 AC: 76338 AN: 152080 Hom.: 19418 Cov.: 33 AF XY: 0.499 AC XY: 37074 AN XY: 74348

Gnomad4 AFR AF: 0.544

Gnomad4 AMR AF: 0.401

Gnomad4 ASJ AF: 0.452

Gnomad4 EAS AF: 0.312

Gnomad4 SAS AF: 0.574

Gnomad4 FIN AF: 0.488

Gnomad4 NFE AF: 0.514

Gnomad4 OTH AF: 0.508

Alfa AF: 0.501 Hom.: 22442

Bravo AF: 0.493

Asia WGS AF: 0.458 AC: 1592 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	3.7
DANN	Benign	0.52
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0

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: rs705867; hg19: chr7-99818927; COSMIC: COSV52781265; COSMIC: COSV52781265;