chr4-155209852-G-A

Variant names:

• chr4-155209852-G-A
• rs10461257
• NM_000910.4:c.-49+783G>A

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+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
• Publications: 3 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=-0.67).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.672 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000910.4. 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
	NPY2R	NM_000910.4	MANE Select	c.-49+783G>A		intron	N/A	NP_000901.1
	NPY2R	NM_001370180.1		c.-49+787G>A		intron	N/A	NP_001357109.1
	NPY2R	NM_001375470.1		c.-48-4040G>A		intron	N/A	NP_001362399.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NPY2R	ENST00000329476.4	TSL:1 MANE Select	c.-49+783G>A		intron	N/A	ENSP00000332591.3
	NPY2R	ENST00000506608.1	TSL:1	c.-49+787G>A		intron	N/A	ENSP00000426366.1
	MAP9-AS1	ENST00000630664.3	TSL:5	n.399+35568G>A		intron	N/A

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

African (AFR) AF: 0.678 AC: 28108 AN: 41432

American (AMR) AF: 0.344 AC: 5246 AN: 15260

Ashkenazi Jewish (ASJ) AF: 0.394 AC: 1366 AN: 3468

East Asian (EAS) AF: 0.675 AC: 3467 AN: 5134

South Asian (SAS) AF: 0.354 AC: 1698 AN: 4802

European-Finnish (FIN) AF: 0.348 AC: 3668 AN: 10534

Middle Eastern (MID) AF: 0.282 AC: 83 AN: 294

European-Non Finnish (NFE) AF: 0.287 AC: 19505 AN: 67928

Other (OTH) AF: 0.385 AC: 811 AN: 2108

Alfa AF: 0.409 Hom.: 6573

Bravo AF: 0.433

Asia WGS AF: 0.508 AC: 1764 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.67
CADD	Benign	3.7
DANN	Benign	0.79
PhyloP100		-0.73
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: rs10461257; hg19: chr4-156131004;