7-100221304-C-T

Variant names:

• chr7-100221304-C-T
• rs705867
• ENST00000710637.1:n.*2353C>T

Variant summary

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

The ENST00000710637.1(ENSG00000292277):​n.*2353C>T variant causes a non coding transcript exon 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: ENSG00000292277 ENST00000710637.1 non_coding_transcript_exon
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0540
• Publications: 20 publications found

Genes affected

ENSG00000292277 (HGNC:):

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

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
PVRIG	NM_001397246.1	c.*53C>T		3_prime_UTR_variant	Exon 5 of 5	ENST00000699088.1	NP_001384175.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ENSG00000292277	ENST00000710637.1	n.*2353C>T		non_coding_transcript_exon_variant	Exon 9 of 9			ENSP00000518392.1
PVRIG	ENST00000699088.1	c.*53C>T		3_prime_UTR_variant	Exon 5 of 5		NM_001397246.1	ENSP00000514123.1
ENSG00000292277	ENST00000710637.1	n.*2353C>T		3_prime_UTR_variant	Exon 9 of 9			ENSP00000518392.1

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

African (AFR) AF: 0.549 AC: 15350 AN: 27942

American (AMR) AF: 0.352 AC: 7803 AN: 22138

Ashkenazi Jewish (ASJ) AF: 0.461 AC: 8641 AN: 18736

East Asian (EAS) AF: 0.335 AC: 12255 AN: 36544

South Asian (SAS) AF: 0.580 AC: 37085 AN: 63936

European-Finnish (FIN) AF: 0.504 AC: 16305 AN: 32382

Middle Eastern (MID) AF: 0.475 AC: 2439 AN: 5134

European-Non Finnish (NFE) AF: 0.511 AC: 496077 AN: 970432

Other (OTH) AF: 0.500 AC: 25929 AN: 51896

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

African (AFR) AF: 0.544 AC: 22547 AN: 41484

American (AMR) AF: 0.401 AC: 6134 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.452 AC: 1566 AN: 3468

East Asian (EAS) AF: 0.312 AC: 1612 AN: 5162

South Asian (SAS) AF: 0.574 AC: 2768 AN: 4822

European-Finnish (FIN) AF: 0.488 AC: 5160 AN: 10576

Middle Eastern (MID) AF: 0.527 AC: 155 AN: 294

European-Non Finnish (NFE) AF: 0.514 AC: 34938 AN: 67960

Other (OTH) AF: 0.508 AC: 1071 AN: 2110

Alfa AF: 0.503 Hom.: 28777

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
PhyloP100		-0.054
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		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: rs705867; hg19: chr7-99818927; COSMIC: COSV52781265; COSMIC: COSV52781265;