4-155214810-G-A

Variant names:

• chr4-155214810-G-A
• rs147783618
• NM_000910.4:c.871G>A

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_000910.4(NPY2R):​c.871G>A​(p.Val291Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000023 in 1,612,088 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 17/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000092 (0 hom., cov: 33)
  • Exomes 𝑓: 0.000016 (0 hom.)
• Consequence: NPY2R NM_000910.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.85
• Publications: 4 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: Likely_benign. The variant received -4 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0586586).

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.871G>A	p.Val291Ile	missense	Exon 2 of 2	NP_000901.1	P49146
	NPY2R	NM_001370180.1		c.871G>A	p.Val291Ile	missense	Exon 2 of 2	NP_001357109.1	P49146
	NPY2R	NM_001375470.1		c.871G>A	p.Val291Ile	missense	Exon 2 of 2	NP_001362399.1	P49146

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NPY2R	ENST00000329476.4	TSL:1 MANE Select	c.871G>A	p.Val291Ile	missense	Exon 2 of 2	ENSP00000332591.3	P49146
	NPY2R	ENST00000506608.1	TSL:1	c.871G>A	p.Val291Ile	missense	Exon 2 of 2	ENSP00000426366.1	P49146
	MAP9-AS1	ENST00000630664.3	TSL:5	n.399+40526G>A		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.0000920 AC: 14 AN: 152176 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.000338

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000399 AC: 10 AN: 250486 AF XY: 0.0000369

Gnomad AFR exome AF: 0.000246

Gnomad AMR exome AF: 0.000145

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00000883

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000158 AC: 23 AN: 1459912 Hom.: 0 Cov.: 42 AF XY: 0.0000179 AC XY: 13 AN XY: 726010

African (AFR) AF: 0.000180 AC: 6 AN: 33396

American (AMR) AF: 0.000112 AC: 5 AN: 44620

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26056

East Asian (EAS) AF: 0.00 AC: 0 AN: 39674

South Asian (SAS) AF: 0.00 AC: 0 AN: 86130

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53360

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5746

European-Non Finnish (NFE) AF: 0.00000900 AC: 10 AN: 1110618

Other (OTH) AF: 0.0000332 AC: 2 AN: 60312

GnomAD4 genome AF: 0.0000920 AC: 14 AN: 152176 Hom.: 0 Cov.: 33 AF XY: 0.0000807 AC XY: 6 AN XY: 74346

African (AFR) AF: 0.000338 AC: 14 AN: 41442

American (AMR) AF: 0.00 AC: 0 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5186

South Asian (SAS) AF: 0.00 AC: 0 AN: 4828

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10618

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 68032

Other (OTH) AF: 0.00 AC: 0 AN: 2092

Alfa AF: 0.000102 Hom.: 0

Bravo AF: 0.0000793

ESP6500AA AF: 0.000227 AC: 1

ESP6500EA AF: 0.00 AC: 0

ExAC AF: 0.0000412 AC: 5

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.098
BayesDel_addAF	Benign	-0.41	T
BayesDel_noAF	Benign	-0.53
CADD	Benign	21
DANN	Benign	0.93
DEOGEN2	Benign	0.070	T
Eigen	Benign	-0.35
Eigen_PC	Benign	-0.16
FATHMM_MKL	Benign	0.65	D
LIST_S2	Uncertain	0.91	D
M_CAP	Benign	0.0054	T
MetaRNN	Benign	0.059	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	-0.090	N
PhyloP100		2.9
PrimateAI	Benign	0.31	T
PROVEAN	Benign	-0.12	N
REVEL	Benign	0.090
Sift	Benign	0.25	T
Sift4G	Benign	0.29	T
Polyphen		0.0040	B
Vest4		0.056
MVP		0.31
MPC		0.25
ClinPred		0.022	T
GERP RS		4.7
Varity_R		0.043
gMVP		0.20
Mutation Taster		=97/3	polymorphism

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: rs147783618; hg19: chr4-156135962; COSMIC: COSV61527760;