7-24284370-G-T

Position:

• chr7-24284370-G-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_000905.4(NPY):​c.-1+95G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.486 in 152,322 control chromosomes in the GnomAD database, including 18,688 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 0.49 (18626 hom., cov: 32)
  • Exomes 𝑓: 0.56 (62 hom.)
• Consequence: NPY NM_000905.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.131

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.649 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NPY	NM_000905.4	c.-1+95G>T		intron_variant		ENST00000242152.7	NP_000896.1
LOC107986777	XR_001745132.2	n.209+34987C>A		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NPY	ENST00000242152.7	c.-1+95G>T		intron_variant		1	NM_000905.4	ENSP00000242152	P1
NPY	ENST00000407573.5	c.-203+95G>T		intron_variant		3		ENSP00000384364	P1

Frequencies

GnomAD3 genomes AF: 0.486 AC: 73808 AN: 151788 Hom.: 18617 Cov.: 32

Gnomad AFR AF: 0.362

Gnomad AMI AF: 0.442

Gnomad AMR AF: 0.604

Gnomad ASJ AF: 0.562

Gnomad EAS AF: 0.668

Gnomad SAS AF: 0.534

Gnomad FIN AF: 0.515

Gnomad MID AF: 0.510

Gnomad NFE AF: 0.510

Gnomad OTH AF: 0.496

GnomAD4 exome AF: 0.563 AC: 234 AN: 416 Hom.: 62 AF XY: 0.579 AC XY: 184 AN XY: 318

Gnomad4 AFR exome AF: 0.500

Gnomad4 ASJ exome AF: 0.500

Gnomad4 EAS exome AF: 0.500

Gnomad4 SAS exome AF: 0.500

Gnomad4 FIN exome AF: 0.667

Gnomad4 NFE exome AF: 0.555

Gnomad4 OTH exome AF: 0.722

GnomAD4 genome AF: 0.486 AC: 73850 AN: 151906 Hom.: 18626 Cov.: 32 AF XY: 0.491 AC XY: 36450 AN XY: 74232

Gnomad4 AFR AF: 0.362

Gnomad4 AMR AF: 0.605

Gnomad4 ASJ AF: 0.562

Gnomad4 EAS AF: 0.668

Gnomad4 SAS AF: 0.535

Gnomad4 FIN AF: 0.515

Gnomad4 NFE AF: 0.510

Gnomad4 OTH AF: 0.494

Alfa AF: 0.500 Hom.: 2464

Bravo AF: 0.488

Asia WGS AF: 0.561 AC: 1951 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	3.6
DANN	Benign	0.55

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

Other links and lift over

dbSNP: rs16145; hg19: chr7-24323989;