7-24285051-A-G

Variant names:

• chr7-24285051-A-G
• rs16142
• NM_000905.4:c.1-190A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_000905.4(NPY):​c.1-190A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.278 in 621,746 control chromosomes in the GnomAD database, including 25,406 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 0.31 (7889 hom., cov: 32)
  • Exomes 𝑓: 0.27 (17517 hom.)
• Consequence: NPY NM_000905.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.481
• Publications: 9 publications found

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]

ENSG00000228944 (HGNC:):

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.8).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.438 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000905.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NPY	NM_000905.4	MANE Select	c.1-190A>G		intron	N/A	NP_000896.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NPY	ENST00000242152.7	TSL:1 MANE Select	c.1-190A>G		intron	N/A	ENSP00000242152.2
	NPY	ENST00000407573.5	TSL:3	c.-26A>G		5_prime_UTR	Exon 2 of 5	ENSP00000384364.1
	ENSG00000228944	ENST00000718234.1		n.319+34306T>C		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.310 AC: 47051 AN: 151812 Hom.: 7869 Cov.: 32

Gnomad AFR AF: 0.443

Gnomad AMI AF: 0.401

Gnomad AMR AF: 0.234

Gnomad ASJ AF: 0.260

Gnomad EAS AF: 0.280

Gnomad SAS AF: 0.321

Gnomad FIN AF: 0.252

Gnomad MID AF: 0.312

Gnomad NFE AF: 0.258

Gnomad OTH AF: 0.312

GnomAD4 exome AF: 0.268 AC: 125716 AN: 469816 Hom.: 17517 Cov.: 5 AF XY: 0.270 AC XY: 66524 AN XY: 246842

African (AFR) AF: 0.443 AC: 5694 AN: 12862

American (AMR) AF: 0.203 AC: 4028 AN: 19820

Ashkenazi Jewish (ASJ) AF: 0.252 AC: 3486 AN: 13828

East Asian (EAS) AF: 0.282 AC: 8742 AN: 30974

South Asian (SAS) AF: 0.316 AC: 14851 AN: 47000

European-Finnish (FIN) AF: 0.231 AC: 6926 AN: 29964

Middle Eastern (MID) AF: 0.342 AC: 690 AN: 2020

European-Non Finnish (NFE) AF: 0.258 AC: 73841 AN: 286686

Other (OTH) AF: 0.280 AC: 7458 AN: 26662

GnomAD4 genome AF: 0.310 AC: 47110 AN: 151930 Hom.: 7889 Cov.: 32 AF XY: 0.308 AC XY: 22884 AN XY: 74290

African (AFR) AF: 0.443 AC: 18369 AN: 41430

American (AMR) AF: 0.233 AC: 3562 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.260 AC: 901 AN: 3472

East Asian (EAS) AF: 0.280 AC: 1437 AN: 5136

South Asian (SAS) AF: 0.320 AC: 1540 AN: 4806

European-Finnish (FIN) AF: 0.252 AC: 2660 AN: 10564

Middle Eastern (MID) AF: 0.322 AC: 94 AN: 292

European-Non Finnish (NFE) AF: 0.258 AC: 17530 AN: 67944

Other (OTH) AF: 0.311 AC: 653 AN: 2102

Alfa AF: 0.289 Hom.: 904

Bravo AF: 0.313

Asia WGS AF: 0.308 AC: 1071 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	7.3
DANN	Benign	0.46
PhyloP100		-0.48
PromoterAI		0.0088	Neutral
Mutation Taster		=300/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.050		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: rs16142; hg19: chr7-24324670; COSMIC: COSV54215563; COSMIC: COSV54215563;