Variant 4-163325337-T-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP4_StrongBP6_Very_StrongBS2

The NM_000909.6(NPY1R):c.1121A>C(p.Lys374Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00626 in 1,611,318 control chromosomes in the GnomAD database, including 51 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

Frequency

Genomes: 𝑓 0.0048 ( 8 hom., cov: 32)

Exomes 𝑓: 0.0064 ( 43 hom. )

Consequence

NPY1R
NM_000909.6 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 2.42

Variant links:

Genes affected

NPY1R (HGNC:7956): (neuropeptide Y receptor Y1) This gene belongs to the G-protein-coupled receptor superfamily. The encoded transmembrane protein mediates the function of neuropeptide Y (NPY), a neurotransmitter, and peptide YY (PYY), a gastrointestinal hormone. The encoded receptor undergoes fast agonist-induced internalization through clathrin-coated pits and is subsequently recycled back to the cell membrane. Activation of Y1 receptors may result in mobilization of intracellular calcium and inhibition of adenylate cyclase activity. [provided by RefSeq, Aug 2013]

NPY1R links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -16 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.005621642).

BP6

Variant 4-163325337-T-G is Benign according to our data. Variant chr4-163325337-T-G is described in ClinVar as [Benign]. Clinvar id is 774176.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS2

High Homozygotes in GnomAd4 at 8 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
NPY1R	NM_000909.6 linkuse as main transcript	c.1121A>C	p.Lys374Thr	missense_variant	3/3	ENST00000296533.3	NP_000900.1
NPY1R	XM_005263031.5 linkuse as main transcript	c.1121A>C	p.Lys374Thr	missense_variant	3/3		XP_005263088.1
NPY1R	XM_011532010.4 linkuse as main transcript	c.1121A>C	p.Lys374Thr	missense_variant	3/3		XP_011530312.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NPY1R	ENST00000296533.3 linkuse as main transcript	c.1121A>C	p.Lys374Thr	missense_variant	3/3	1	NM_000909.6	ENSP00000354652	P1
NPY1R	ENST00000509586.5 linkuse as main transcript	c.392A>C	p.Lys131Thr	missense_variant	4/4	2		ENSP00000427284

Frequencies

GnomAD3 genomes

AF:

0.00480

AC:

731

AN:

152230

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00142

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00582

Gnomad ASJ

AF:

0.0135

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00269

Gnomad FIN

AF:

0.00103

Gnomad MID

AF:

0.0127

Gnomad NFE

AF:

0.00726

Gnomad OTH

AF:

0.00669

GnomAD3 exomes

AF:

0.00507

AC:

1263

AN:

248876

Hom.:

AF XY:

0.00528

AC XY:

710

AN XY:

134502

show subpopulations

Gnomad AFR exome

AF:

0.00105

Gnomad AMR exome

AF:

0.00423

Gnomad ASJ exome

AF:

0.0122

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00315

Gnomad FIN exome

AF:

0.00232

Gnomad NFE exome

AF:

0.00703

Gnomad OTH exome

AF:

0.00714

GnomAD4 exome

AF:

0.00641

AC:

9352

AN:

1458970

Hom.:

Cov.:

AF XY:

0.00634

AC XY:

4599

AN XY:

725712

show subpopulations

Gnomad4 AFR exome

AF:

0.000816

Gnomad4 AMR exome

AF:

0.00506

Gnomad4 ASJ exome

AF:

0.0128

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00320

Gnomad4 FIN exome

AF:

0.00245

Gnomad4 NFE exome

AF:

0.00715

Gnomad4 OTH exome

AF:

0.00623

GnomAD4 genome

AF:

0.00480

AC:

731

AN:

152348

Hom.:

Cov.:

AF XY:

0.00462

AC XY:

344

AN XY:

74516

show subpopulations

Gnomad4 AFR

AF:

0.00142

Gnomad4 AMR

AF:

0.00582

Gnomad4 ASJ

AF:

0.0135

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00290

Gnomad4 FIN

AF:

0.00103

Gnomad4 NFE

AF:

0.00726

Gnomad4 OTH

AF:

0.00662

Alfa

AF:

0.00755

Hom.:

Bravo

AF:

0.00488

TwinsUK

AF:

0.00674

AC:

ALSPAC

AF:

0.00545

AC:

ESP6500AA

AF:

0.00113

AC:

ESP6500EA

AF:

0.00709

AC:

ExAC

AF:

0.00467

AC:

567

Asia WGS

AF:

0.000289

AC:

AN:

3478

EpiCase

AF:

0.0106

EpiControl

AF:

0.0100

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jul 06, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.094

BayesDel_addAF

Benign

-0.32

BayesDel_noAF

Benign

-0.23

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Benign

0.089

T;.

Eigen

Benign

-0.12

Eigen_PC

Benign

0.035

FATHMM_MKL

Uncertain

0.94

LIST_S2

Benign

0.58

T;T

M_CAP

Benign

0.019

MetaRNN

Benign

0.0056

T;T

MetaSVM

Benign

-0.90

MutationAssessor

Benign

1.2

L;.

MutationTaster

Benign

0.79

D;D

PrimateAI

Uncertain

0.59

PROVEAN

Benign

0.29

N;N

REVEL

Benign

0.22

Sift

Uncertain

0.017

D;D

Sift4G

Benign

0.21

T;D

Polyphen

0.42

B;.

Vest4

0.33

MVP

0.71

MPC

0.99

ClinPred

0.024

GERP RS

3.1

Varity_R

0.13

gMVP

0.48

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

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