6-152753187-C-T

Position:

• chr6-152753187-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_003381.4(VIP):​c.107+903C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.281 in 151,922 control chromosomes in the GnomAD database, including 7,874 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 0.28 (7874 hom., cov: 32)
• Consequence: VIP NM_003381.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.35

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.519 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
VIP	NM_003381.4	c.107+903C>T		intron_variant		ENST00000367244.8	NP_003372.1
VIP	NM_194435.3	c.107+903C>T		intron_variant			NP_919416.1
VIP	XM_006715562.5	c.107+903C>T		intron_variant			XP_006715625.1
VIP	XM_005267135.4	c.107+903C>T		intron_variant			XP_005267192.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
VIP	ENST00000367244.8	c.107+903C>T		intron_variant		1	NM_003381.4	ENSP00000356213.3
VIP	ENST00000367243.7	c.107+903C>T		intron_variant		1		ENSP00000356212.3

Frequencies

GnomAD3 genomes AF: 0.281 AC: 42627 AN: 151802 Hom.: 7840 Cov.: 32

Gnomad AFR AF: 0.524

Gnomad AMI AF: 0.214

Gnomad AMR AF: 0.201

Gnomad ASJ AF: 0.296

Gnomad EAS AF: 0.0934

Gnomad SAS AF: 0.215

Gnomad FIN AF: 0.189

Gnomad MID AF: 0.341

Gnomad NFE AF: 0.184

Gnomad OTH AF: 0.284

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.281 AC: 42709 AN: 151922 Hom.: 7874 Cov.: 32 AF XY: 0.277 AC XY: 20592 AN XY: 74262

Gnomad4 AFR AF: 0.525

Gnomad4 AMR AF: 0.200

Gnomad4 ASJ AF: 0.296

Gnomad4 EAS AF: 0.0934

Gnomad4 SAS AF: 0.216

Gnomad4 FIN AF: 0.189

Gnomad4 NFE AF: 0.184

Gnomad4 OTH AF: 0.282

Alfa AF: 0.204 Hom.: 7557

Bravo AF: 0.292

Asia WGS AF: 0.184 AC: 642 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.032
DANN	Benign	0.43

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

Other links and lift over

dbSNP: rs3823082; hg19: chr6-153074322; COSMIC: COSV65888706; COSMIC: COSV65888706;