Genetic Variant NM_003381.4:c.342C>G (chr6-152756140-C-G) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_003381.4(VIP):c.342C>G(p.Asn114Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000706 in 1,416,884 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. N114N) has been classified as Likely benign.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 7.1e-7 ( 0 hom. )

Consequence

VIP
NM_003381.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.347

Publications

0 publications found

Variant links:

Genes affected

VIP (HGNC:12693): (vasoactive intestinal peptide) The protein encoded by this gene belongs to the glucagon family. It stimulates myocardial contractility, causes vasodilation, increases glycogenolysis, lowers arterial blood pressure and relaxes the smooth muscle of trachea, stomach and gall bladder. The protein also acts as an antimicrobial peptide with antibacterial and antifungal activity. Alternative splicing occurs at this locus and two transcript variants encoding distinct isoforms have been identified. [provided by RefSeq, Nov 2014]

VIP links:

LINC02840 (HGNC:54374): (long intergenic non-protein coding RNA 2840)

LINC02840 links:

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ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.052648008).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_003381.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
VIP	NM_003381.4	MANE Select	c.342C>G	p.Asn114Lys	missense	Exon 5 of 7	NP_003372.1	P01282-1
VIP	NM_194435.3		c.339C>G	p.Asn113Lys	missense	Exon 5 of 7	NP_919416.1	P01282-2
LINC02840	NR_183504.1		n.3130G>C		non_coding_transcript_exon	Exon 4 of 4

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
VIP	ENST00000367244.8	TSL:1 MANE Select	c.342C>G	p.Asn114Lys	missense	Exon 5 of 7	ENSP00000356213.3	P01282-1
VIP	ENST00000367243.7	TSL:1	c.339C>G	p.Asn113Lys	missense	Exon 5 of 7	ENSP00000356212.3	P01282-2
VIP	ENST00000897584.1		c.342C>G	p.Asn114Lys	missense	Exon 5 of 7	ENSP00000567643.1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

7.06e-7

AC:

AN:

1416884

Hom.:

Cov.:

AF XY:

0.00000142

AC XY:

AN XY:

703286

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

31278

American (AMR)

AF:

0.00

AC:

AN:

39208

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

24316

East Asian (EAS)

AF:

0.00

AC:

AN:

38372

South Asian (SAS)

AF:

0.00

AC:

AN:

76410

European-Finnish (FIN)

AF:

0.00

AC:

AN:

51956

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5526

European-Non Finnish (NFE)

AF:

9.16e-7

AC:

AN:

1091586

Other (OTH)

AF:

0.00

AC:

AN:

58232

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.425

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

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.19

BayesDel_addAF

Benign

-0.29

BayesDel_noAF

Benign

-0.65

CADD

Benign

(source)

DANN

Benign

0.87

DEOGEN2

Uncertain

0.53

Eigen

Benign

-0.74

Eigen_PC

Benign

-0.76

FATHMM_MKL

Benign

0.41

LIST_S2

Benign

0.81

M_CAP

Benign

0.0079

MetaRNN

Benign

0.053

MetaSVM

Benign

-0.97

MutationAssessor

Uncertain

2.3

PhyloP100

0.35

PrimateAI

Benign

0.30

PROVEAN

Benign

-1.8

REVEL

Benign

0.024

Sift

Benign

0.12

Sift4G

Benign

0.40

Polyphen

0.046

Vest4

0.086

MutPred

0.35

Gain of ubiquitination at N114 (P = 0.0101)

MVP

0.014

MPC

0.16

ClinPred

0.063

GERP RS

2.4

Varity_R

0.10

gMVP

0.070

Mutation Taster

=95/5

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

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

ClinVar

Computational scores

Splicing

Publications

Other links and lift over