NM_000910.4:c.-49+2226G>C

Variant names:

• chr4-155211295-G-C
• rs10461239
• NM_000910.4:c.-49+2226G>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+2226G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.115 in 152,132 control chromosomes in the GnomAD database, including 1,619 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 0.11 (1619 hom., cov: 32)
• Consequence: NPY2R NM_000910.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.00700
• 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=-0.86).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.478 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NPY2R	NM_000910.4	MANE Select	c.-49+2226G>C		intron	N/A	NP_000901.1
	NPY2R	NM_001370180.1		c.-49+2230G>C		intron	N/A	NP_001357109.1
	NPY2R	NM_001375470.1		c.-48-2597G>C		intron	N/A	NP_001362399.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NPY2R	ENST00000329476.4	TSL:1 MANE Select	c.-49+2226G>C		intron	N/A	ENSP00000332591.3
	NPY2R	ENST00000506608.1	TSL:1	c.-49+2230G>C		intron	N/A	ENSP00000426366.1
	MAP9-AS1	ENST00000630664.3	TSL:5	n.399+37011G>C		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.115 AC: 17416 AN: 152014 Hom.: 1606 Cov.: 32

Gnomad AFR AF: 0.149

Gnomad AMI AF: 0.00658

Gnomad AMR AF: 0.183

Gnomad ASJ AF: 0.0937

Gnomad EAS AF: 0.495

Gnomad SAS AF: 0.166

Gnomad FIN AF: 0.112

Gnomad MID AF: 0.0701

Gnomad NFE AF: 0.0496

Gnomad OTH AF: 0.0955

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

GnomAD4 genome AF: 0.115 AC: 17453 AN: 152132 Hom.: 1619 Cov.: 32 AF XY: 0.121 AC XY: 8991 AN XY: 74366

African (AFR) AF: 0.149 AC: 6165 AN: 41502

American (AMR) AF: 0.184 AC: 2812 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.0937 AC: 325 AN: 3470

East Asian (EAS) AF: 0.494 AC: 2549 AN: 5156

South Asian (SAS) AF: 0.164 AC: 792 AN: 4816

European-Finnish (FIN) AF: 0.112 AC: 1189 AN: 10584

Middle Eastern (MID) AF: 0.0719 AC: 21 AN: 292

European-Non Finnish (NFE) AF: 0.0496 AC: 3374 AN: 68004

Other (OTH) AF: 0.104 AC: 220 AN: 2116

Alfa AF: 0.0273 Hom.: 18

Bravo AF: 0.121

Asia WGS AF: 0.322 AC: 1116 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	2.2
DANN	Benign	0.56
PhyloP100		-0.0070
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: rs10461239; hg19: chr4-156132447;