19-53258520-C-T

Variant names:

• chr19-53258520-C-T
• rs140171943
• NM_173856.2:c.145C>T

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_Strong BP6_Moderate BS2

The NM_173856.2(VN1R2):​c.145C>T​(p.Arg49Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00499 in 1,467,742 control chromosomes in the GnomAD database, including 32 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0042 (4 hom., cov: 32)
  • Exomes 𝑓: 0.0051 (28 hom.)
• Consequence: VN1R2 NM_173856.2 missense
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.254
• Publications: 4 publications found

Genes affected

VN1R2 (HGNC:19872): (vomeronasal 1 receptor 2) Predicted to enable pheromone receptor activity. Predicted to be involved in G protein-coupled receptor signaling pathway and response to pheromone. Predicted to be located in plasma membrane. Predicted to be integral component of membrane. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Benign. The variant received -10 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.004188299).
• BP6: Variant 19-53258520-C-T is Benign according to our data. Variant chr19-53258520-C-T is described in ClinVar as Likely_benign. ClinVar VariationId is 2650409.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High Homozygotes in GnomAd4 at 4 AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_173856.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	VN1R2	NM_173856.2	MANE Select	c.145C>T	p.Arg49Cys	missense	Exon 1 of 1	NP_776255.2	Q8NFZ6

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	VN1R2	ENST00000341702.3	TSL:6 MANE Select	c.145C>T	p.Arg49Cys	missense	Exon 1 of 1	ENSP00000351244.2	Q8NFZ6

Frequencies

GnomAD3 genomes AF: 0.00424 AC: 646 AN: 152182 Hom.: 4 Cov.: 32

Gnomad AFR AF: 0.00118

Gnomad AMI AF: 0.00110

Gnomad AMR AF: 0.00288

Gnomad ASJ AF: 0.0156

Gnomad EAS AF: 0.000193

Gnomad SAS AF: 0.000414

Gnomad FIN AF: 0.00122

Gnomad MID AF: 0.00633

Gnomad NFE AF: 0.00697

Gnomad OTH AF: 0.00287

GnomAD2 exomes AF: 0.00370 AC: 576 AN: 155586 AF XY: 0.00372

Gnomad AFR exome AF: 0.00133

Gnomad AMR exome AF: 0.00210

Gnomad ASJ exome AF: 0.00859

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00286

Gnomad NFE exome AF: 0.00595

Gnomad OTH exome AF: 0.00596

GnomAD4 exome AF: 0.00508 AC: 6682 AN: 1315442 Hom.: 28 Cov.: 22 AF XY: 0.00509 AC XY: 3328 AN XY: 653208

African (AFR) AF: 0.00113 AC: 34 AN: 30022

American (AMR) AF: 0.00290 AC: 103 AN: 35574

Ashkenazi Jewish (ASJ) AF: 0.0109 AC: 268 AN: 24638

East Asian (EAS) AF: 0.0000566 AC: 2 AN: 35338

South Asian (SAS) AF: 0.000516 AC: 40 AN: 77594

European-Finnish (FIN) AF: 0.00189 AC: 93 AN: 49282

Middle Eastern (MID) AF: 0.000997 AC: 4 AN: 4014

European-Non Finnish (NFE) AF: 0.00586 AC: 5882 AN: 1003908

Other (OTH) AF: 0.00465 AC: 256 AN: 55072

GnomAD4 genome AF: 0.00424 AC: 645 AN: 152300 Hom.: 4 Cov.: 32 AF XY: 0.00408 AC XY: 304 AN XY: 74476

African (AFR) AF: 0.00118 AC: 49 AN: 41562

American (AMR) AF: 0.00288 AC: 44 AN: 15302

Ashkenazi Jewish (ASJ) AF: 0.0156 AC: 54 AN: 3468

East Asian (EAS) AF: 0.000193 AC: 1 AN: 5174

South Asian (SAS) AF: 0.000415 AC: 2 AN: 4822

European-Finnish (FIN) AF: 0.00122 AC: 13 AN: 10626

Middle Eastern (MID) AF: 0.00680 AC: 2 AN: 294

European-Non Finnish (NFE) AF: 0.00695 AC: 473 AN: 68026

Other (OTH) AF: 0.00284 AC: 6 AN: 2116

Alfa AF: 0.00619 Hom.: 2

Bravo AF: 0.00423

TwinsUK AF: 0.00728 AC: 27

ALSPAC AF: 0.00441 AC: 17

ESP6500AA AF: 0.000249 AC: 1

ESP6500EA AF: 0.00542 AC: 42

ExAC AF: 0.00167 AC: 129

Asia WGS AF: 0.00144 AC: 5 AN: 3478

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.14
BayesDel_addAF	Benign	-0.59	T
BayesDel_noAF	Benign	-0.62
CADD	Benign	15
DANN	Benign	0.49
DEOGEN2	Benign	0.00076	T
Eigen	Benign	-0.74
Eigen_PC	Benign	-0.98
FATHMM_MKL	Benign	0.0021	N
LIST_S2	Benign	0.40	T
MetaRNN	Benign	0.0042	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.0	N
PhyloP100		-0.25
PrimateAI	Uncertain	0.51	T
PROVEAN	Benign	-0.040	N
REVEL	Benign	0.079
Sift	Pathogenic	0.0	D
Polyphen		0.98	D
Vest4		0.24
MVP		0.13
MPC		0.17
ClinPred		0.027	T
GERP RS		0.046
PromoterAI		0.0069	Neutral
Varity_R		0.13
gMVP		0.38
Mutation Taster		=100/0	polymorphism

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: rs140171943; hg19: chr19-53761773; COSMIC: COSV104631492; COSMIC: COSV104631492;