chr7-24289514-C-T

Variant names:

• chr7-24289514-C-T
• rs5574
• NM_000905.4:c.204C>T

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_Moderate BP6_Moderate BP7 BA1

The NM_000905.4(NPY):​c.204C>T​(p.Ser68Ser) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.458 in 1,585,064 control chromosomes in the GnomAD database, including 169,337 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.43 (14177 hom., cov: 30)
  • Exomes 𝑓: 0.46 (155160 hom.)
• Consequence: NPY NM_000905.4 synonymous
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.357
• Publications: 54 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 -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.4).
• BP6: Variant 7-24289514-C-T is Benign according to our data. Variant chr7-24289514-C-T is described in ClinVar as Benign. ClinVar VariationId is 1601323.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=-0.357 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.474 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NPY	NM_000905.4	MANE Select	c.204C>T	p.Ser68Ser	synonymous	Exon 3 of 4	NP_000896.1	P01303

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NPY	ENST00000242152.7	TSL:1 MANE Select	c.204C>T	p.Ser68Ser	synonymous	Exon 3 of 4	ENSP00000242152.2	P01303
	NPY	ENST00000405982.1	TSL:1	c.204C>T	p.Ser68Ser	synonymous	Exon 2 of 3	ENSP00000385282.1	P01303
	NPY	ENST00000407573.5	TSL:3	c.204C>T	p.Ser68Ser	synonymous	Exon 4 of 5	ENSP00000384364.1	P01303

Frequencies

GnomAD3 genomes AF: 0.428 AC: 64873 AN: 151484 Hom.: 14178 Cov.: 30

Gnomad AFR AF: 0.348

Gnomad AMI AF: 0.441

Gnomad AMR AF: 0.430

Gnomad ASJ AF: 0.490

Gnomad EAS AF: 0.361

Gnomad SAS AF: 0.344

Gnomad FIN AF: 0.465

Gnomad MID AF: 0.487

Gnomad NFE AF: 0.478

Gnomad OTH AF: 0.433

GnomAD2 exomes AF: 0.429 AC: 100479 AN: 234306 AF XY: 0.426

Gnomad AFR exome AF: 0.347

Gnomad AMR exome AF: 0.436

Gnomad ASJ exome AF: 0.478

Gnomad EAS exome AF: 0.345

Gnomad FIN exome AF: 0.470

Gnomad NFE exome AF: 0.466

Gnomad OTH exome AF: 0.438

GnomAD4 exome AF: 0.461 AC: 661128 AN: 1433462 Hom.: 155160 Cov.: 32 AF XY: 0.458 AC XY: 326353 AN XY: 712992

African (AFR) AF: 0.342 AC: 10992 AN: 32132

American (AMR) AF: 0.441 AC: 18128 AN: 41132

Ashkenazi Jewish (ASJ) AF: 0.487 AC: 12422 AN: 25506

East Asian (EAS) AF: 0.320 AC: 12300 AN: 38490

South Asian (SAS) AF: 0.332 AC: 27087 AN: 81688

European-Finnish (FIN) AF: 0.470 AC: 24756 AN: 52702

Middle Eastern (MID) AF: 0.425 AC: 2419 AN: 5690

European-Non Finnish (NFE) AF: 0.480 AC: 526738 AN: 1096936

Other (OTH) AF: 0.444 AC: 26286 AN: 59186

GnomAD4 genome AF: 0.428 AC: 64891 AN: 151602 Hom.: 14177 Cov.: 30 AF XY: 0.425 AC XY: 31457 AN XY: 74056

African (AFR) AF: 0.347 AC: 14331 AN: 41284

American (AMR) AF: 0.431 AC: 6574 AN: 15248

Ashkenazi Jewish (ASJ) AF: 0.490 AC: 1697 AN: 3464

East Asian (EAS) AF: 0.359 AC: 1846 AN: 5136

South Asian (SAS) AF: 0.343 AC: 1642 AN: 4790

European-Finnish (FIN) AF: 0.465 AC: 4867 AN: 10464

Middle Eastern (MID) AF: 0.497 AC: 145 AN: 292

European-Non Finnish (NFE) AF: 0.478 AC: 32486 AN: 67908

Other (OTH) AF: 0.428 AC: 902 AN: 2106

Alfa AF: 0.464 Hom.: 21264

Bravo AF: 0.424

Asia WGS AF: 0.296 AC: 1033 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.40
CADD	Benign	2.4
DANN	Benign	0.64
PhyloP100		-0.36
Mutation Taster		=99/1	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
Splicevardb		2.0
SpliceAI score (max)		0.14		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: rs5574; hg19: chr7-24329133; COSMIC: COSV54215144;