rs10461257

chr4-155209852-G-A

Variant summary

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

The NM_000910.4(NPY2R):c.-49+783G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.423 in 151,872 control chromosomes in the GnomAD database, including 15,768 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 0.42 (15768 hom., cov: 31)
• Consequence: NPY2R NM_000910.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.726

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

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.67).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.672 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NPY2R	NM_000910.4	c.-49+783G>A		intron_variant		ENST00000329476.4
NPY2R	NM_001370180.1	c.-49+787G>A		intron_variant
NPY2R	NM_001375470.1	c.-48-4040G>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NPY2R	ENST00000329476.4	c.-49+783G>A		intron_variant		1	NM_000910.4	P1
NPY2R	ENST00000506608.1	c.-49+787G>A		intron_variant		1		P1
MAP9-AS1	ENST00000630664.2	n.208+35568G>A		intron_variant, non_coding_transcript_variant		5

Frequencies

GnomAD3 genomes AF: 0.422 AC: 64092 AN: 151756 Hom.: 15749 Cov.: 31

Gnomad AFR AF: 0.679

Gnomad AMI AF: 0.239

Gnomad AMR AF: 0.344

Gnomad ASJ AF: 0.394

Gnomad EAS AF: 0.676

Gnomad SAS AF: 0.355

Gnomad FIN AF: 0.348

Gnomad MID AF: 0.291

Gnomad NFE AF: 0.287

Gnomad OTH AF: 0.378

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

GnomAD4 genome AF: 0.423 AC: 64170 AN: 151872 Hom.: 15768 Cov.: 31 AF XY: 0.423 AC XY: 31410 AN XY: 74202

Gnomad4 AFR AF: 0.678

Gnomad4 AMR AF: 0.344

Gnomad4 ASJ AF: 0.394

Gnomad4 EAS AF: 0.675

Gnomad4 SAS AF: 0.354

Gnomad4 FIN AF: 0.348

Gnomad4 NFE AF: 0.287

Gnomad4 OTH AF: 0.385

Alfa AF: 0.348 Hom.: 2142

Bravo AF: 0.433

Asia WGS AF: 0.508 AC: 1764 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.67
Cadd	Benign	3.7
Dann	Benign	0.79

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: rs10461257; hg19: chr4-156131004;