7-24285260-T-C

Position:

chr7-24285260-T-C

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBS1BS2

The NM_000905.4(NPY):c.20T>C(p.Leu7Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0332 in 1,614,018 control chromosomes in the GnomAD database, including 1,045 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.027 ( 85 hom., cov: 32)

Exomes 𝑓: 0.034 ( 960 hom. )

Consequence

NPY
NM_000905.4 missense

Scores

Clinical Significance

Benign criteria provided, single submitter B:2

Conservation

PhyloP100: 3.31

Variant links:

Genes affected

NPY (HGNC:7955): (neuropeptide Y) This gene encodes a neuropeptide that is widely expressed in the central nervous system and influences many physiological processes, including cortical excitability, stress response, food intake, circadian rhythms, and cardiovascular function. The neuropeptide functions through G protein-coupled receptors to inhibit adenylyl cyclase, activate mitogen-activated protein kinase (MAPK), regulate intracellular calcium levels, and activate potassium channels. A polymorphism in this gene resulting in a change of leucine 7 to proline in the signal peptide is associated with elevated cholesterol levels, higher alcohol consumption, and may be a risk factor for various metabolic and cardiovascular diseases. The protein also exhibits antimicrobial activity against bacteria and fungi. [provided by RefSeq, Oct 2014]

NPY links:

LOC107986777 (HGNC:):

LOC107986777 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -14 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0022782385).

BP6

Variant 7-24285260-T-C is Benign according to our data. Variant chr7-24285260-T-C is described in ClinVar as [Benign]. Clinvar id is 14024.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr7-24285260-T-C is described in Lovd as [Benign].

BS1

Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.0272 (4144/152250) while in subpopulation NFE AF= 0.0383 (2602/68012). AF 95% confidence interval is 0.037. There are 85 homozygotes in gnomad4. There are 2105 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High AC in GnomAd4 at 4144 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NPY	NM_000905.4 linkuse as main transcript	c.20T>C	p.Leu7Pro	missense_variant	2/4	ENST00000242152.7
LOC107986777	XR_001745132.2 linkuse as main transcript	n.209+34097A>G		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris
NPY	ENST00000242152.7 linkuse as main transcript	c.20T>C	p.Leu7Pro	missense_variant	2/4	1	NM_000905.4	P1
NPY	ENST00000405982.1 linkuse as main transcript	c.20T>C	p.Leu7Pro	missense_variant	1/3	1		P1
NPY	ENST00000407573.5 linkuse as main transcript	c.20T>C	p.Leu7Pro	missense_variant	3/5	3		P1

Frequencies

GnomAD3 genomes

AF:

0.0273

AC:

4146

AN:

152132

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00630

Gnomad AMI

AF:

0.0219

Gnomad AMR

AF:

0.0209

Gnomad ASJ

AF:

0.0110

Gnomad EAS

AF:

0.000193

Gnomad SAS

AF:

0.0326

Gnomad FIN

AF:

0.0643

Gnomad MID

AF:

0.0253

Gnomad NFE

AF:

0.0382

Gnomad OTH

AF:

0.0278

GnomAD3 exomes

AF:

0.0298

AC:

7467

AN:

250628

Hom.:

147

AF XY:

0.0310

AC XY:

4194

AN XY:

135490

show subpopulations

Gnomad AFR exome

AF:

0.00696

Gnomad AMR exome

AF:

0.0164

Gnomad ASJ exome

AF:

0.0118

Gnomad EAS exome

AF:

0.000109

Gnomad SAS exome

AF:

0.0316

Gnomad FIN exome

AF:

0.0629

Gnomad NFE exome

AF:

0.0364

Gnomad OTH exome

AF:

0.0378

GnomAD4 exome

AF:

0.0338

AC:

49382

AN:

1461768

Hom.:

960

Cov.:

AF XY:

0.0338

AC XY:

24547

AN XY:

727202

show subpopulations

Gnomad4 AFR exome

AF:

0.00520

Gnomad4 AMR exome

AF:

0.0167

Gnomad4 ASJ exome

AF:

0.0107

Gnomad4 EAS exome

AF:

0.000176

Gnomad4 SAS exome

AF:

0.0323

Gnomad4 FIN exome

AF:

0.0663

Gnomad4 NFE exome

AF:

0.0358

Gnomad4 OTH exome

AF:

0.0319

GnomAD4 genome

AF:

0.0272

AC:

4144

AN:

152250

Hom.:

Cov.:

AF XY:

0.0283

AC XY:

2105

AN XY:

74444

show subpopulations

Gnomad4 AFR

AF:

0.00628

Gnomad4 AMR

AF:

0.0208

Gnomad4 ASJ

AF:

0.0110

Gnomad4 EAS

AF:

0.000194

Gnomad4 SAS

AF:

0.0324

Gnomad4 FIN

AF:

0.0643

Gnomad4 NFE

AF:

0.0383

Gnomad4 OTH

AF:

0.0275

Alfa

AF:

0.0319

Hom.:

193

Bravo

AF:

0.0219

TwinsUK

AF:

0.0313

AC:

116

ALSPAC

AF:

0.0304

AC:

117

ESP6500AA

AF:

0.00885

AC:

ESP6500EA

AF:

0.0362

AC:

311

ExAC

AF:

0.0302

AC:

3670

Asia WGS

AF:

0.0100

AC:

AN:

3478

EpiCase

AF:

0.0338

EpiControl

AF:

0.0312

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Jan 22, 2024

- -

NEUROPEPTIDE Y POLYMORPHISM

Benign:1

Benign, no assertion criteria provided

literature only

OMIM

Jul 01, 2003

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.092

BayesDel_addAF

Benign

-0.52

BayesDel_noAF

Benign

-0.49

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Benign

0.13

T;T;T

Eigen

Benign

-0.017

Eigen_PC

Benign

0.16

FATHMM_MKL

Uncertain

0.87

LIST_S2

Benign

0.66

.;.;T

MetaRNN

Benign

0.0023

T;T;T

MetaSVM

Benign

-1.1

MutationTaster

Benign

1.0

D;D;D

PrimateAI

Uncertain

0.48

PROVEAN

Benign

1.8

N;N;N

REVEL

Benign

0.084

Sift

Benign

0.16

T;T;T

Sift4G

Uncertain

0.060

T;T;T

Polyphen

0.0

B;B;B

Vest4

0.42

MPC

2.0

ClinPred

0.029

GERP RS

5.6

Varity_R

0.37

gMVP

0.56

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over