NM_000910.4:c.-49+1995G>C

Variant names:

• chr4-155211064-G-C
• rs10461238
• NM_000910.4:c.-49+1995G>C

Variant summary

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

The NM_000910.4(NPY2R):​c.-49+1995G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.517 in 151,988 control chromosomes in the GnomAD database, including 21,520 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 0.52 (21520 hom., cov: 32)
• Consequence: NPY2R NM_000910.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.861
• Publications: 5 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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.738 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NPY2R	NM_000910.4	c.-49+1995G>C		intron_variant	Intron 1 of 1	ENST00000329476.4	NP_000901.1
NPY2R	NM_001370180.1	c.-49+1999G>C		intron_variant	Intron 1 of 1		NP_001357109.1
NPY2R	NM_001375470.1	c.-48-2828G>C		intron_variant	Intron 1 of 1		NP_001362399.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NPY2R	ENST00000329476.4	c.-49+1995G>C		intron_variant	Intron 1 of 1	1	NM_000910.4	ENSP00000332591.3
NPY2R	ENST00000506608.1	c.-49+1999G>C		intron_variant	Intron 1 of 1	1		ENSP00000426366.1
MAP9-AS1	ENST00000630664.3	n.399+36780G>C		intron_variant	Intron 2 of 4	5

Frequencies

GnomAD3 genomes AF: 0.517 AC: 78443 AN: 151870 Hom.: 21506 Cov.: 32

Gnomad AFR AF: 0.670

Gnomad AMI AF: 0.555

Gnomad AMR AF: 0.425

Gnomad ASJ AF: 0.422

Gnomad EAS AF: 0.758

Gnomad SAS AF: 0.516

Gnomad FIN AF: 0.555

Gnomad MID AF: 0.396

Gnomad NFE AF: 0.426

Gnomad OTH AF: 0.465

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

GnomAD4 genome AF: 0.517 AC: 78504 AN: 151988 Hom.: 21520 Cov.: 32 AF XY: 0.522 AC XY: 38761 AN XY: 74264

African (AFR) AF: 0.670 AC: 27761 AN: 41460

American (AMR) AF: 0.426 AC: 6504 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.422 AC: 1463 AN: 3468

East Asian (EAS) AF: 0.758 AC: 3914 AN: 5166

South Asian (SAS) AF: 0.514 AC: 2478 AN: 4818

European-Finnish (FIN) AF: 0.555 AC: 5852 AN: 10536

Middle Eastern (MID) AF: 0.391 AC: 115 AN: 294

European-Non Finnish (NFE) AF: 0.426 AC: 28918 AN: 67954

Other (OTH) AF: 0.471 AC: 993 AN: 2108

Alfa AF: 0.487 Hom.: 2250

Bravo AF: 0.510

Asia WGS AF: 0.665 AC: 2311 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	0.60
DANN	Benign	0.63
PhyloP100		-0.86
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: rs10461238; hg19: chr4-156132216;