rs17376826

Positions:

• chr4-155209796-C-T

Variant summary

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

The NM_000910.4(NPY2R):​c.-49+727C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0701 in 151,928 control chromosomes in the GnomAD database, including 448 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 0.070 (448 hom., cov: 32)
• Consequence: NPY2R NM_000910.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.748

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=-0.89).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.116 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NPY2R	NM_000910.4	c.-49+727C>T		intron_variant		ENST00000329476.4	NP_000901.1
NPY2R	NM_001370180.1	c.-49+731C>T		intron_variant			NP_001357109.1
NPY2R	NM_001375470.1	c.-48-4096C>T		intron_variant			NP_001362399.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NPY2R	ENST00000329476.4	c.-49+727C>T		intron_variant		1	NM_000910.4	ENSP00000332591	P1
NPY2R	ENST00000506608.1	c.-49+731C>T		intron_variant		1		ENSP00000426366	P1
MAP9-AS1	ENST00000630664.2	n.208+35512C>T		intron_variant, non_coding_transcript_variant		5

Frequencies

GnomAD3 genomes AF: 0.0699 AC: 10610 AN: 151810 Hom.: 442 Cov.: 32

Gnomad AFR AF: 0.118

Gnomad AMI AF: 0.0430

Gnomad AMR AF: 0.0646

Gnomad ASJ AF: 0.0590

Gnomad EAS AF: 0.000193

Gnomad SAS AF: 0.0141

Gnomad FIN AF: 0.0284

Gnomad MID AF: 0.123

Gnomad NFE AF: 0.0574

Gnomad OTH AF: 0.0876

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

GnomAD4 genome AF: 0.0701 AC: 10645 AN: 151928 Hom.: 448 Cov.: 32 AF XY: 0.0677 AC XY: 5028 AN XY: 74256

Gnomad4 AFR AF: 0.119

Gnomad4 AMR AF: 0.0645

Gnomad4 ASJ AF: 0.0590

Gnomad4 EAS AF: 0.000194

Gnomad4 SAS AF: 0.0135

Gnomad4 FIN AF: 0.0284

Gnomad4 NFE AF: 0.0574

Gnomad4 OTH AF: 0.0867

Alfa AF: 0.0620 Hom.: 343

Bravo AF: 0.0760

Asia WGS AF: 0.0220 AC: 77 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	1.2
DANN	Benign	0.53

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: rs17376826; hg19: chr4-156130948;