Genetic Variant NPY:p.Ala28Ala (chr7-24285324-G-A) – ACMG Classification: Benign (-15 pts)

Variant summary

Our verdict is Benign. The variant received -15 ACMG points: 0P and 15B. BP4_StrongBP6_ModerateBP7BA1

The NM_000905.4(NPY):c.84G>A(p.Ala28Ala) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00346 in 1,614,016 control chromosomes in the GnomAD database, including 172 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.018 ( 94 hom., cov: 32)

Exomes 𝑓: 0.0019 ( 78 hom. )

Consequence

NPY
NM_000905.4 synonymous

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -1.17

Publications

7 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:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -15 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.47).

BP6

Variant 7-24285324-G-A is Benign according to our data. Variant chr7-24285324-G-A is described in ClinVar as Benign. ClinVar VariationId is 776210.Status of the report is criteria_provided_single_submitter, 1 stars.

BP7

Synonymous conserved (PhyloP=-1.17 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0615 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.84G>A	p.Ala28Ala	synonymous	Exon 2 of 4	NP_000896.1	P01303

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
NPY	ENST00000242152.7	TSL:1 MANE Select	c.84G>A	p.Ala28Ala	synonymous	Exon 2 of 4	ENSP00000242152.2	P01303
NPY	ENST00000405982.1	TSL:1	c.84G>A	p.Ala28Ala	synonymous	Exon 1 of 3	ENSP00000385282.1	P01303
NPY	ENST00000407573.5	TSL:3	c.84G>A	p.Ala28Ala	synonymous	Exon 3 of 5	ENSP00000384364.1	P01303

Frequencies

GnomAD3 genomes

AF:

0.0180

AC:

2745

AN:

152106

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0632

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00510

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000622

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00633

Gnomad NFE

AF:

0.000162

Gnomad OTH

AF:

0.0158

GnomAD2 exomes

AF:

0.00446

AC:

1120

AN:

251002

AF XY:

0.00320

show subpopulations

Gnomad AFR exome

AF:

0.0598

Gnomad AMR exome

AF:

0.00353

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0000544

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000106

Gnomad OTH exome

AF:

0.00196

GnomAD4 exome

AF:

0.00192

AC:

2811

AN:

1461792

Hom.:

Cov.:

AF XY:

0.00166

AC XY:

1205

AN XY:

727212

show subpopulations

African (AFR)

AF:

0.0670

AC:

2243

AN:

33480

American (AMR)

AF:

0.00373

AC:

167

AN:

44718

Ashkenazi Jewish (ASJ)

AF:

0.0000383

AC:

AN:

26124

East Asian (EAS)

AF:

0.00

AC:

AN:

39698

South Asian (SAS)

AF:

0.000128

AC:

AN:

86254

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53362

Middle Eastern (MID)

AF:

0.00451

AC:

AN:

5766

European-Non Finnish (NFE)

AF:

0.0000647

AC:

AN:

1111998

Other (OTH)

AF:

0.00482

AC:

291

AN:

60392

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.487

Heterozygous variant carriers

154

309

463

618

772

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

152

228

304

380

<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:

0.0182

AC:

2766

AN:

152224

Hom.:

Cov.:

AF XY:

0.0177

AC XY:

1315

AN XY:

74436

show subpopulations

African (AFR)

AF:

0.0635

AC:

2639

AN:

41530

American (AMR)

AF:

0.00510

AC:

AN:

15300

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5164

South Asian (SAS)

AF:

0.000623

AC:

AN:

4816

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10610

Middle Eastern (MID)

AF:

0.00680

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.000162

AC:

AN:

68020

Other (OTH)

AF:

0.0156

AC:

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

134

268

401

535

669

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

120

<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:

0.00839

Hom.:

Bravo

AF:

0.0202

Asia WGS

AF:

0.00491

AC:

AN:

3478

EpiCase

AF:

0.000164

EpiControl

AF:

0.000119

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.47

CADD

Benign

9.5

(source)

DANN

Benign

0.93

PhyloP100

-1.2

PromoterAI

0.015

Neutral

(source)

Mutation Taster

=98/2

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