Genetic Variant NPY:p.Ser68Ser (chr7-24289514-C-T) – ACMG Classification: Benign (-13 pts)

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_ModerateBP6_ModerateBP7BA1

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

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.357

Publications

54 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 -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NPY	NM_000905.4 link	c.204C>T	p.Ser68Ser	synonymous_variant	Exon 3 of 4	ENST00000242152.7	NP_000896.1	P01303A4D158

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NPY	ENST00000242152.7 link	c.204C>T	p.Ser68Ser	synonymous_variant	Exon 3 of 4	1	NM_000905.4	ENSP00000242152.2		P01303

Frequencies

GnomAD3 genomes

AF:

0.428

AC:

64873

AN:

151484

Hom.:

14178

Cov.:

show subpopulations

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

show subpopulations

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.:

AF XY:

0.458

AC XY:

326353

AN XY:

712992

show subpopulations

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

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.444

Heterozygous variant carriers

16256

32512

48769

65025

81281

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

15520

31040

46560

62080

77600

<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:

0.428

AC:

64891

AN:

151602

Hom.:

14177

Cov.:

AF XY:

0.425

AC XY:

31457

AN XY:

74056

show subpopulations

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

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

1849

3698

5546

7395

9244

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

628

1256

1884

2512

3140

<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:

0.464

Hom.:

21264

Bravo

AF:

0.424

Asia WGS

AF:

0.296

AC:

1033

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.40

CADD

Benign

2.4

(source)

DANN

Benign

0.64

PhyloP100

-0.36

Mutation Taster

=99/1

polymorphism (auto)

(source)

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

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

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over