Genetic Variant ENSG00000228944:n.319+27459A>G (chr7-24291898-T-C) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The ENST00000718234.1(ENSG00000228944):n.319+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

ENSG00000228944
ENST00000718234.1 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.319

Publications

3 publications found

Variant links:

Genes affected

ENSG00000228944 (HGNC:):

ENSG00000228944 links:

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]

NPY links:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -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 link	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 link	c.*211T>C		downstream_gene_variant		1	NM_000905.4	ENSP00000242152.2

Frequencies

GnomAD3 genomes

AF:

0.0407

AC:

6199

AN:

152156

Hom.:

401

Cov.:

show subpopulations

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.:

AF XY:

0.00433

AC XY:

885

AN XY:

204556

show subpopulations

African (AFR)

AF:

0.143

AC:

1493

AN:

10444

American (AMR)

AF:

0.0122

AC:

146

AN:

11920

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

12186

East Asian (EAS)

AF:

0.00

AC:

AN:

27250

South Asian (SAS)

AF:

0.000456

AC:

AN:

30726

European-Finnish (FIN)

AF:

0.00

AC:

AN:

28272

Middle Eastern (MID)

AF:

0.00327

AC:

AN:

2140

European-Non Finnish (NFE)

AF:

0.000254

AC:

AN:

244188

Other (OTH)

AF:

0.0126

AC:

288

AN:

22910

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

156

234

312

390

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

110

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0409

AC:

6231

AN:

152274

Hom.:

407

Cov.:

AF XY:

0.0397

AC XY:

2953

AN XY:

74456

show subpopulations

African (AFR)

AF:

0.142

AC:

5877

AN:

41530

American (AMR)

AF:

0.0178

AC:

272

AN:

15292

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5186

South Asian (SAS)

AF:

0.00

AC:

AN:

4826

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10616

Middle Eastern (MID)

AF:

0.00340

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.000323

AC:

AN:

68034

Other (OTH)

AF:

0.0279

AC:

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

265

529

794

1058

1323

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

128

192

256

320

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0221

Hom.:

Bravo

AF:

0.0466

Asia WGS

AF:

0.00895

AC:

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

(source)

DANN

Benign

0.54

PhyloP100

0.32

Splicing

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

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over