Genetic Variant VIP:p.Asn133Asn (chr6-152756197-C-T) – ACMG Classification: Benign (-15 pts)

Variant summary

Our verdict is Benign. Variant got -15 ACMG points: 0P and 15B. BP4_StrongBP6_ModerateBP7BS1BS2

The NM_003381.4(VIP):c.399C>T(p.Asn133Asn) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00636 in 1,611,734 control chromosomes in the GnomAD database, including 150 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.013 ( 30 hom., cov: 32)

Exomes 𝑓: 0.0056 ( 120 hom. )

Consequence

VIP
NM_003381.4 synonymous

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 2.05

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 made for transcript

Verdict is Benign. Variant got -15 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.49).

BP6

Variant 6-152756197-C-T is Benign according to our data. Variant chr6-152756197-C-T is described in ClinVar as [Benign]. Clinvar id is 774186.Status of the report is criteria_provided_single_submitter, 1 stars.

BP7

Synonymous conserved (PhyloP=2.05 with no splicing effect.

BS1

Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.0134 (2035/152052) while in subpopulation AFR AF= 0.0279 (1159/41518). AF 95% confidence interval is 0.0266. There are 30 homozygotes in gnomad4. There are 996 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 30 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
VIP	NM_003381.4 link	c.399C>T	p.Asn133Asn	synonymous_variant	Exon 5 of 7	ENST00000367244.8	NP_003372.1	P01282-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
VIP	ENST00000367244.8 link	c.399C>T	p.Asn133Asn	synonymous_variant	Exon 5 of 7	1	NM_003381.4	ENSP00000356213.3	P01282-1
VIP	ENST00000367243.7 link	c.396C>T	p.Asn132Asn	synonymous_variant	Exon 5 of 7	1		ENSP00000356212.3	P01282-2
VIP	ENST00000431366.1 link	c.246C>T	p.Asn82Asn	synonymous_variant	Exon 3 of 5	3		ENSP00000410356.1	H0Y763
LINC02840	ENST00000666093.1 link	n.3124G>A		non_coding_transcript_exon_variant	Exon 5 of 5

Frequencies

GnomAD3 genomes

AF:

0.0134

AC:

2032

AN:

151934

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0279

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0183

Gnomad ASJ

AF:

0.0571

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00332

Gnomad FIN

AF:

0.00132

Gnomad MID

AF:

0.0538

Gnomad NFE

AF:

0.00440

Gnomad OTH

AF:

0.0259

GnomAD3 exomes

AF:

0.00955

AC:

2391

AN:

250340

Hom.:

AF XY:

0.00919

AC XY:

1244

AN XY:

135330

show subpopulations

Gnomad AFR exome

AF:

0.0298

Gnomad AMR exome

AF:

0.0124

Gnomad ASJ exome

AF:

0.0580

Gnomad EAS exome

AF:

0.0000545

Gnomad SAS exome

AF:

0.00583

Gnomad FIN exome

AF:

0.00157

Gnomad NFE exome

AF:

0.00516

Gnomad OTH exome

AF:

0.0171

GnomAD4 exome

AF:

0.00562

AC:

8208

AN:

1459682

Hom.:

120

Cov.:

AF XY:

0.00582

AC XY:

4225

AN XY:

726150

show subpopulations

Gnomad4 AFR exome

AF:

0.0299

Gnomad4 AMR exome

AF:

0.0130

Gnomad4 ASJ exome

AF:

0.0564

Gnomad4 EAS exome

AF:

0.0000504

Gnomad4 SAS exome

AF:

0.00567

Gnomad4 FIN exome

AF:

0.00154

Gnomad4 NFE exome

AF:

0.00310

Gnomad4 OTH exome

AF:

0.0139

GnomAD4 genome

AF:

0.0134

AC:

2035

AN:

152052

Hom.:

Cov.:

AF XY:

0.0134

AC XY:

996

AN XY:

74354

show subpopulations

Gnomad4 AFR

AF:

0.0279

Gnomad4 AMR

AF:

0.0183

Gnomad4 ASJ

AF:

0.0571

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00332

Gnomad4 FIN

AF:

0.00132

Gnomad4 NFE

AF:

0.00440

Gnomad4 OTH

AF:

0.0256

Alfa

AF:

0.0124

Hom.:

Bravo

AF:

0.0155

Asia WGS

AF:

0.00520

AC:

AN:

3478

EpiCase

AF:

0.00855

EpiControl

AF:

0.00850

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Dec 31, 2019

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

-0.49

CADD

Benign

DANN

Benign

0.34

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over