Genetic Variant NPY:c.-1+95G>T (chr7-24284370-G-T) – ACMG Classification: Benign (-12 pts)

Variant summary

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

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

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.131

Publications

6 publications found

Variant links:

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]

NPY links:

ENSG00000228944 (HGNC:):

ENSG00000228944 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=-0.86).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.649 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NPY	NM_000905.4	MANE Select	c.-1+95G>T		intron	N/A	NP_000896.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein
NPY	ENST00000242152.7	TSL:1 MANE Select	c.-1+95G>T	intron	N/A	ENSP00000242152.2
NPY	ENST00000407573.5	TSL:3	c.-203+95G>T	intron	N/A	ENSP00000384364.1
ENSG00000228944	ENST00000718234.1		n.319+34987C>A	intron	N/A

Frequencies

GnomAD3 genomes

AF:

0.486

AC:

73808

AN:

151788

Hom.:

18617

Cov.:

show subpopulations

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.:

AF XY:

0.579

AC XY:

184

AN XY:

318

show subpopulations

African (AFR)

AF:

0.500

AC:

AN:

American (AMR)

AC:

AN:

Ashkenazi Jewish (ASJ)

AF:

0.500

AC:

AN:

East Asian (EAS)

AF:

0.500

AC:

AN:

South Asian (SAS)

AF:

0.500

AC:

AN:

European-Finnish (FIN)

AF:

0.667

AC:

AN:

Middle Eastern (MID)

AF:

0.500

AC:

AN:

European-Non Finnish (NFE)

AF:

0.555

AC:

202

AN:

364

Other (OTH)

AF:

0.722

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.470

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<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:

0.486

AC:

73850

AN:

151906

Hom.:

18626

Cov.:

AF XY:

0.491

AC XY:

36450

AN XY:

74232

show subpopulations

African (AFR)

AF:

0.362

AC:

15003

AN:

41472

American (AMR)

AF:

0.605

AC:

9247

AN:

15286

Ashkenazi Jewish (ASJ)

AF:

0.562

AC:

1946

AN:

3464

East Asian (EAS)

AF:

0.668

AC:

3418

AN:

5120

South Asian (SAS)

AF:

0.535

AC:

2571

AN:

4810

European-Finnish (FIN)

AF:

0.515

AC:

5438

AN:

10558

Middle Eastern (MID)

AF:

0.510

AC:

149

AN:

292

European-Non Finnish (NFE)

AF:

0.510

AC:

34633

AN:

67882

Other (OTH)

AF:

0.494

AC:

1044

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.496

Heterozygous variant carriers

1842

3684

5527

7369

9211

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

680

1360

2040

2720

3400

<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:

0.496

Hom.:

2514

Bravo

AF:

0.488

Asia WGS

AF:

0.561

AC:

1951

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.86

CADD

Benign

3.6

(source)

DANN

Benign

0.55

PhyloP100

0.13

PromoterAI

-0.063

Neutral

(source)

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over