7-24284969-C-T

Variant names:

• chr7-24284969-C-T
• rs16143
• NM_000905.4:c.1-272C>T

Variant summary

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

The NM_000905.4(NPY):​c.1-272C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.271 in 547,464 control chromosomes in the GnomAD database, including 21,115 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 0.29 (6964 hom., cov: 32)
  • Exomes 𝑓: 0.26 (14151 hom.)
• Consequence: NPY NM_000905.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0230
• Publications: 6 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=-0.77).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.39 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.1-272C>T		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.1-272C>T		intron	N/A	ENSP00000242152.2
	NPY	ENST00000407573.5	TSL:3	c.-108C>T		5_prime_UTR	Exon 2 of 5	ENSP00000384364.1
	ENSG00000228944	ENST00000718234.1		n.319+34388G>A		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.295 AC: 44824 AN: 152006 Hom.: 6952 Cov.: 32

Gnomad AFR AF: 0.395

Gnomad AMI AF: 0.402

Gnomad AMR AF: 0.231

Gnomad ASJ AF: 0.245

Gnomad EAS AF: 0.278

Gnomad SAS AF: 0.299

Gnomad FIN AF: 0.252

Gnomad MID AF: 0.313

Gnomad NFE AF: 0.257

Gnomad OTH AF: 0.302

GnomAD4 exome AF: 0.262 AC: 103569 AN: 395340 Hom.: 14151 Cov.: 2 AF XY: 0.263 AC XY: 54552 AN XY: 207188

African (AFR) AF: 0.391 AC: 4248 AN: 10870

American (AMR) AF: 0.201 AC: 3184 AN: 15842

Ashkenazi Jewish (ASJ) AF: 0.240 AC: 2949 AN: 12272

East Asian (EAS) AF: 0.278 AC: 7296 AN: 26256

South Asian (SAS) AF: 0.289 AC: 12125 AN: 41988

European-Finnish (FIN) AF: 0.230 AC: 5955 AN: 25938

Middle Eastern (MID) AF: 0.327 AC: 568 AN: 1736

European-Non Finnish (NFE) AF: 0.257 AC: 60943 AN: 237338

Other (OTH) AF: 0.273 AC: 6301 AN: 23100

GnomAD4 genome AF: 0.295 AC: 44873 AN: 152124 Hom.: 6964 Cov.: 32 AF XY: 0.293 AC XY: 21799 AN XY: 74366

African (AFR) AF: 0.395 AC: 16393 AN: 41488

American (AMR) AF: 0.230 AC: 3518 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.245 AC: 852 AN: 3472

East Asian (EAS) AF: 0.278 AC: 1434 AN: 5154

South Asian (SAS) AF: 0.299 AC: 1440 AN: 4824

European-Finnish (FIN) AF: 0.252 AC: 2665 AN: 10586

Middle Eastern (MID) AF: 0.323 AC: 95 AN: 294

European-Non Finnish (NFE) AF: 0.257 AC: 17474 AN: 67986

Other (OTH) AF: 0.301 AC: 636 AN: 2112

Alfa AF: 0.275 Hom.: 771

Bravo AF: 0.296

Asia WGS AF: 0.299 AC: 1040 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.77
CADD	Benign	6.6
DANN	Benign	0.80
PhyloP100		-0.023
PromoterAI		-0.017	Neutral
Mutation Taster		=299/1	polymorphism (auto)

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

Other links and lift over

dbSNP: rs16143; hg19: chr7-24324588;