Genetic Variant NPY2R:c.-48-5487A>G (chr4-155208405-A-G) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_001375470.1(NPY2R):c.-48-5487A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.226 in 152,208 control chromosomes in the GnomAD database, including 4,433 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 0.23 ( 4426 hom., cov: 32)

Exomes 𝑓: 0.24 ( 7 hom. )

Consequence

NPY2R
NM_001375470.1 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.320

Publications

13 publications found

Variant links:

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]

NPY2R links:

NPY2R-AS1 (HGNC:55549): (NPY2R antisense RNA 1)

NPY2R-AS1 links:

MAP9-AS1 (HGNC:56110): (MAP9 antisense RNA 1)

MAP9-AS1 links:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.81).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.49 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001375470.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
NPY2R	NM_001375470.1		c.-48-5487A>G	intron	N/A	NP_001362399.1	P49146
NPY2R	NM_000910.4	MANE Select	c.-713A>G	upstream_gene	N/A	NP_000901.1	P49146
NPY2R	NM_001370180.1		c.-709A>G	upstream_gene	N/A	NP_001357109.1	P49146

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank
NPY2R-AS1	ENST00000511017.7	TSL:3	n.150T>C	non_coding_transcript_exon	Exon 1 of 3
NPY2R-AS1	ENST00000727158.1		n.38T>C	non_coding_transcript_exon	Exon 1 of 5
NPY2R-AS1	ENST00000727159.1		n.82T>C	non_coding_transcript_exon	Exon 1 of 5

Frequencies

GnomAD3 genomes

AF:

0.226

AC:

34367

AN:

151906

Hom.:

4428

Cov.:

show subpopulations

Gnomad AFR

AF:

0.161

Gnomad AMI

AF:

0.191

Gnomad AMR

AF:

0.299

Gnomad ASJ

AF:

0.150

Gnomad EAS

AF:

0.506

Gnomad SAS

AF:

0.421

Gnomad FIN

AF:

0.272

Gnomad MID

AF:

0.152

Gnomad NFE

AF:

0.212

Gnomad OTH

AF:

0.233

GnomAD4 exome

AF:

0.242

AC:

AN:

186

Hom.:

Cov.:

AF XY:

0.238

AC XY:

AN XY:

130

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

American (AMR)

AC:

AN:

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

East Asian (EAS)

AF:

0.250

AC:

AN:

South Asian (SAS)

AF:

0.750

AC:

AN:

European-Finnish (FIN)

AF:

0.333

AC:

AN:

Middle Eastern (MID)

AC:

AN:

European-Non Finnish (NFE)

AF:

0.228

AC:

AN:

158

Other (OTH)

AF:

0.375

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.528

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.226

AC:

34359

AN:

152022

Hom.:

4426

Cov.:

AF XY:

0.237

AC XY:

17609

AN XY:

74274

show subpopulations

African (AFR)

AF:

0.160

AC:

6661

AN:

41510

American (AMR)

AF:

0.299

AC:

4566

AN:

15280

Ashkenazi Jewish (ASJ)

AF:

0.150

AC:

521

AN:

3472

East Asian (EAS)

AF:

0.506

AC:

2580

AN:

5096

South Asian (SAS)

AF:

0.419

AC:

2019

AN:

4814

European-Finnish (FIN)

AF:

0.272

AC:

2874

AN:

10572

Middle Eastern (MID)

AF:

0.150

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.212

AC:

14438

AN:

67964

Other (OTH)

AF:

0.229

AC:

482

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.505

Heterozygous variant carriers

1347

2694

4041

5388

6735

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

376

752

1128

1504

1880

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.179

Hom.:

1087

Bravo

AF:

0.220

Asia WGS

AF:

0.431

AC:

1498

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.81

CADD

Benign

3.1

(source)

DANN

Benign

0.68

PhyloP100

-0.32

PromoterAI

0.033

Neutral

(source)

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over