7-24290218-T-C

Variant names:

• chr7-24290218-T-C
• rs16131
• NM_000905.4:c.269+639T>C

Variant summary

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

The NM_000905.4(NPY):​c.269+639T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.114 in 152,168 control chromosomes in the GnomAD database, including 1,056 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 0.11 (1056 hom., cov: 31)
• Consequence: NPY NM_000905.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.711
• Publications: 10 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=-0.86).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.143 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NPY	NM_000905.4	c.269+639T>C		intron_variant	Intron 3 of 3	ENST00000242152.7	NP_000896.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NPY	ENST00000242152.7	c.269+639T>C		intron_variant	Intron 3 of 3	1	NM_000905.4	ENSP00000242152.2

Frequencies

GnomAD3 genomes AF: 0.114 AC: 17280 AN: 152052 Hom.: 1056 Cov.: 31

Gnomad AFR AF: 0.0768

Gnomad AMI AF: 0.112

Gnomad AMR AF: 0.101

Gnomad ASJ AF: 0.148

Gnomad EAS AF: 0.0467

Gnomad SAS AF: 0.0693

Gnomad FIN AF: 0.114

Gnomad MID AF: 0.108

Gnomad NFE AF: 0.145

Gnomad OTH AF: 0.115

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.114 AC: 17275 AN: 152168 Hom.: 1056 Cov.: 31 AF XY: 0.111 AC XY: 8270 AN XY: 74402

African (AFR) AF: 0.0767 AC: 3184 AN: 41518

American (AMR) AF: 0.101 AC: 1542 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.148 AC: 515 AN: 3470

East Asian (EAS) AF: 0.0466 AC: 241 AN: 5170

South Asian (SAS) AF: 0.0694 AC: 335 AN: 4830

European-Finnish (FIN) AF: 0.114 AC: 1205 AN: 10584

Middle Eastern (MID) AF: 0.105 AC: 31 AN: 294

European-Non Finnish (NFE) AF: 0.145 AC: 9881 AN: 67978

Other (OTH) AF: 0.113 AC: 239 AN: 2112

Alfa AF: 0.136 Hom.: 3577

Bravo AF: 0.113

Asia WGS AF: 0.0630 AC: 220 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	0.81
DANN	Benign	0.66
PhyloP100		-0.71
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		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: rs16131; hg19: chr7-24329837;