7-24285260-T-C

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BS1 BS2

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
• Clinical Significance: Benign criteria provided, single submitter B:2
• Conservation: PhyloP100: 3.31

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]

LOC107986777 (HGNC:):

ACMG classification

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 GnomAd at 4146 AD gene.

Transcripts

RefSeq

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

Ensembl

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

Frequencies

GnomAD3 genomes AF: 0.0273 AC: 4146 AN: 152132 Hom.: 85 Cov.: 32

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

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.: 32 AF XY: 0.0338 AC XY: 24547 AN XY: 727202

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.: 85 Cov.: 32 AF XY: 0.0283 AC XY: 2105 AN XY: 74444

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: 39

ESP6500EA AF: 0.0362 AC: 311

ExAC AF: 0.0302 AC: 3670

Asia WGS AF: 0.0100 AC: 35 AN: 3478

EpiCase AF: 0.0338

EpiControl AF: 0.0312

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

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	T
BayesDel_noAF	Benign	-0.49
Cadd	Uncertain	25
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	D
MetaRNN	Benign	0.0023	T;T;T
MetaSVM	Benign	-1.1	T
MutationTaster	Benign	1.0	D;D;D
PrimateAI	Uncertain	0.48	T
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	T
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

Other links and lift over

dbSNP: rs16139; hg19: chr7-24324879; COSMIC: COSV54215688;