4-155214524-C-T

Variant names:

• chr4-155214524-C-T
• rs1047214
• NM_000910.4:c.585C>T

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

The NM_000910.4(NPY2R):​c.585C>T​(p.Ile195Ile) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.565 in 1,613,844 control chromosomes in the GnomAD database, including 264,995 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 0.65 (34015 hom., cov: 32)
  • Exomes 𝑓: 0.56 (230980 hom.)
• Consequence: NPY2R NM_000910.4 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.85
• Publications: 40 publications found

Genes affected

NPY2R (HGNC:7957): (neuropeptide Y receptor Y2) Predicted to enable calcium channel regulator activity and neuropeptide Y receptor activity. Involved in cardiac left ventricle morphogenesis and outflow tract morphogenesis. Located in cilium. Implicated in Huntington's disease; morbid obesity; and obesity. Biomarker of peripheral artery disease and temporal lobe epilepsy. [provided by Alliance of Genome Resources, Apr 2022]

MAP9-AS1 (HGNC:56110): (MAP9 antisense RNA 1)

ACMG classification

Our verdict: Benign. The variant received -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BP7: Synonymous conserved (PhyloP=-1.85 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.874 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NPY2R	NM_000910.4	c.585C>T	p.Ile195Ile	synonymous_variant	Exon 2 of 2	ENST00000329476.4	NP_000901.1
NPY2R	NM_001370180.1	c.585C>T	p.Ile195Ile	synonymous_variant	Exon 2 of 2		NP_001357109.1
NPY2R	NM_001375470.1	c.585C>T	p.Ile195Ile	synonymous_variant	Exon 2 of 2		NP_001362399.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NPY2R	ENST00000329476.4	c.585C>T	p.Ile195Ile	synonymous_variant	Exon 2 of 2	1	NM_000910.4	ENSP00000332591.3
NPY2R	ENST00000506608.1	c.585C>T	p.Ile195Ile	synonymous_variant	Exon 2 of 2	1		ENSP00000426366.1
MAP9-AS1	ENST00000630664.3	n.399+40240C>T		intron_variant	Intron 2 of 4	5

Frequencies

GnomAD3 genomes AF: 0.649 AC: 98713 AN: 151988 Hom.: 33975 Cov.: 32

Gnomad AFR AF: 0.881

Gnomad AMI AF: 0.683

Gnomad AMR AF: 0.515

Gnomad ASJ AF: 0.488

Gnomad EAS AF: 0.796

Gnomad SAS AF: 0.574

Gnomad FIN AF: 0.628

Gnomad MID AF: 0.566

Gnomad NFE AF: 0.545

Gnomad OTH AF: 0.606

GnomAD2 exomes AF: 0.578 AC: 145348 AN: 251388 AF XY: 0.573

Gnomad AFR exome AF: 0.888

Gnomad AMR exome AF: 0.458

Gnomad ASJ exome AF: 0.484

Gnomad EAS exome AF: 0.798

Gnomad FIN exome AF: 0.628

Gnomad NFE exome AF: 0.540

Gnomad OTH exome AF: 0.549

GnomAD4 exome AF: 0.557 AC: 813610 AN: 1461738 Hom.: 230980 Cov.: 50 AF XY: 0.556 AC XY: 404092 AN XY: 727174

African (AFR) AF: 0.898 AC: 30064 AN: 33480

American (AMR) AF: 0.470 AC: 21016 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.487 AC: 12725 AN: 26134

East Asian (EAS) AF: 0.793 AC: 31487 AN: 39700

South Asian (SAS) AF: 0.560 AC: 48292 AN: 86254

European-Finnish (FIN) AF: 0.618 AC: 33002 AN: 53404

Middle Eastern (MID) AF: 0.537 AC: 3096 AN: 5768

European-Non Finnish (NFE) AF: 0.539 AC: 599629 AN: 1111882

Other (OTH) AF: 0.568 AC: 34299 AN: 60392

GnomAD4 genome AF: 0.650 AC: 98809 AN: 152106 Hom.: 34015 Cov.: 32 AF XY: 0.651 AC XY: 48379 AN XY: 74338

African (AFR) AF: 0.881 AC: 36598 AN: 41528

American (AMR) AF: 0.516 AC: 7877 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.488 AC: 1696 AN: 3472

East Asian (EAS) AF: 0.795 AC: 4096 AN: 5154

South Asian (SAS) AF: 0.572 AC: 2751 AN: 4810

European-Finnish (FIN) AF: 0.628 AC: 6639 AN: 10576

Middle Eastern (MID) AF: 0.561 AC: 165 AN: 294

European-Non Finnish (NFE) AF: 0.545 AC: 37083 AN: 67980

Other (OTH) AF: 0.610 AC: 1287 AN: 2110

Alfa AF: 0.577 Hom.: 78497

Bravo AF: 0.649

Asia WGS AF: 0.720 AC: 2502 AN: 3478

EpiCase AF: 0.528

EpiControl AF: 0.525

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	0.91
DANN	Benign	0.65
PhyloP100		-1.9
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: rs1047214; hg19: chr4-156135676; COSMIC: COSV108136031;