7-24291898-T-C

Variant names:

• chr7-24291898-T-C
• rs16126
• XR_001745121.2:n.209+27459A>G

Variant summary

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

The XR_001745121.2(LOC107986777):​n.209+27459A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0152 in 542,310 control chromosomes in the GnomAD database, including 545 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 0.041 (407 hom., cov: 32)
  • Exomes 𝑓: 0.0052 (138 hom.)
• Consequence: LOC107986777 XR_001745121.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.319

Genes affected

LOC107986777 (HGNC:):

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.138 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NPY	NM_000905.4	c.*211T>C		downstream_gene_variant		ENST00000242152.7	NP_000896.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NPY	ENST00000242152.7	c.*211T>C		downstream_gene_variant		1	NM_000905.4	ENSP00000242152.2
NPY	ENST00000405982.1	c.*211T>C		downstream_gene_variant		1		ENSP00000385282.1
NPY	ENST00000407573.5	c.*211T>C		downstream_gene_variant		3		ENSP00000384364.1

Frequencies

GnomAD3 genomes AF: 0.0407 AC: 6199 AN: 152156 Hom.: 401 Cov.: 32

Gnomad AFR AF: 0.141

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0179

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.000323

Gnomad OTH AF: 0.0282

GnomAD4 exome AF: 0.00515 AC: 2010 AN: 390036 Hom.: 138 Cov.: 5 AF XY: 0.00433 AC XY: 885 AN XY: 204556

Gnomad4 AFR exome AF: 0.143

Gnomad4 AMR exome AF: 0.0122

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000456

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.000254

Gnomad4 OTH exome AF: 0.0126

GnomAD4 genome AF: 0.0409 AC: 6231 AN: 152274 Hom.: 407 Cov.: 32 AF XY: 0.0397 AC XY: 2953 AN XY: 74456

Gnomad4 AFR AF: 0.142

Gnomad4 AMR AF: 0.0178

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000323

Gnomad4 OTH AF: 0.0279

Alfa AF: 0.0251 Hom.: 49

Bravo AF: 0.0466

Asia WGS AF: 0.00895 AC: 31 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	3.3
DANN	Benign	0.54

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs16126; hg19: chr7-24331517;