7-24289484-C-CT

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_Moderate BA1

The NM_000905.4(NPY):c.189-5dup variant causes a splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.158 in 1,327,044 control chromosomes in the GnomAD database, including 6,782 homozygotes. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.12 (1112 hom., cov: 30)
  • Exomes 𝑓: 0.16 (5670 hom.)
• Consequence: NPY NM_000905.4 splice_polypyrimidine_tract, intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.00900

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 -10 ACMG points.

• BP6: Variant 7-24289484-C-CT is Benign according to our data. Variant chr7-24289484-C-CT is described in ClinVar as [Benign]. Clinvar id is 1665605.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.145 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NPY	NM_000905.4	c.189-5dup		splice_polypyrimidine_tract_variant, intron_variant		ENST00000242152.7
LOC107986777	XR_001745132.2	n.209+29872_209+29873insA		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NPY	ENST00000242152.7	c.189-5dup		splice_polypyrimidine_tract_variant, intron_variant		1	NM_000905.4	P1
NPY	ENST00000405982.1	c.189-5dup		splice_polypyrimidine_tract_variant, intron_variant		1		P1
NPY	ENST00000407573.5	c.189-5dup		splice_polypyrimidine_tract_variant, intron_variant		3		P1

Frequencies

GnomAD3 genomes AF: 0.119 AC: 17885 AN: 150260 Hom.: 1112 Cov.: 30

Gnomad AFR AF: 0.0876

Gnomad AMI AF: 0.113

Gnomad AMR AF: 0.104

Gnomad ASJ AF: 0.158

Gnomad EAS AF: 0.0594

Gnomad SAS AF: 0.0776

Gnomad FIN AF: 0.116

Gnomad MID AF: 0.111

Gnomad NFE AF: 0.147

Gnomad OTH AF: 0.120

GnomAD3 exomes AF: 0.158 AC: 25810 AN: 162948 Hom.: 533 AF XY: 0.160 AC XY: 14130 AN XY: 88446

Gnomad AFR exome AF: 0.121

Gnomad AMR exome AF: 0.106

Gnomad ASJ exome AF: 0.198

Gnomad EAS exome AF: 0.101

Gnomad SAS exome AF: 0.130

Gnomad FIN exome AF: 0.169

Gnomad NFE exome AF: 0.183

Gnomad OTH exome AF: 0.185

GnomAD4 exome AF: 0.164 AC: 192445 AN: 1176676 Hom.: 5670 Cov.: 27 AF XY: 0.162 AC XY: 95080 AN XY: 585584

Gnomad4 AFR exome AF: 0.102

Gnomad4 AMR exome AF: 0.0845

Gnomad4 ASJ exome AF: 0.173

Gnomad4 EAS exome AF: 0.0662

Gnomad4 SAS exome AF: 0.110

Gnomad4 FIN exome AF: 0.141

Gnomad4 NFE exome AF: 0.177

Gnomad4 OTH exome AF: 0.161

GnomAD4 genome AF: 0.119 AC: 17882 AN: 150368 Hom.: 1112 Cov.: 30 AF XY: 0.117 AC XY: 8547 AN XY: 73332

Gnomad4 AFR AF: 0.0874

Gnomad4 AMR AF: 0.104

Gnomad4 ASJ AF: 0.158

Gnomad4 EAS AF: 0.0593

Gnomad4 SAS AF: 0.0778

Gnomad4 FIN AF: 0.116

Gnomad4 NFE AF: 0.147

Gnomad4 OTH AF: 0.118

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Jan 31, 2024

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Computational scores

Source: dbNSFP v4.3

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: rs35313836; hg19: chr7-24329103;