rs688136

Positions:

• chr6-152758926-T-C

Variant summary

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

The NM_003381.4(VIP):​c.*60T>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.409 in 152,158 control chromosomes in the GnomAD database, including 13,436 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 0.41 (13422 hom., cov: 33)
  • Exomes 𝑓: 0.35 (14 hom.)
• Consequence: VIP NM_003381.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.74

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]

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

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 = 0.55 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
VIP	NM_003381.4	c.*60T>C		3_prime_UTR_variant	7/7	ENST00000367244.8	NP_003372.1
LINC02840	NR_183504.1	n.480-136A>G		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
VIP	ENST00000367244.8	c.*60T>C		3_prime_UTR_variant	7/7	1	NM_003381.4	ENSP00000356213	P4
LINC02840	ENST00000666093.1	n.531-136A>G		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes AF: 0.409 AC: 62081 AN: 151760 Hom.: 13396 Cov.: 33

Gnomad AFR AF: 0.556

Gnomad AMI AF: 0.352

Gnomad AMR AF: 0.324

Gnomad ASJ AF: 0.376

Gnomad EAS AF: 0.151

Gnomad SAS AF: 0.358

Gnomad FIN AF: 0.375

Gnomad MID AF: 0.459

Gnomad NFE AF: 0.370

Gnomad OTH AF: 0.392

GnomAD4 exome AF: 0.355 AC: 100 AN: 282 Hom.: 14 Cov.: 0 AF XY: 0.335 AC XY: 55 AN XY: 164

Gnomad4 FIN exome AF: 0.356

Gnomad4 OTH exome AF: 0.250

GnomAD4 genome AF: 0.409 AC: 62150 AN: 151876 Hom.: 13422 Cov.: 33 AF XY: 0.406 AC XY: 30149 AN XY: 74222

Gnomad4 AFR AF: 0.556

Gnomad4 AMR AF: 0.323

Gnomad4 ASJ AF: 0.376

Gnomad4 EAS AF: 0.151

Gnomad4 SAS AF: 0.360

Gnomad4 FIN AF: 0.375

Gnomad4 NFE AF: 0.370

Gnomad4 OTH AF: 0.390

Alfa AF: 0.377 Hom.: 14240

Bravo AF: 0.412

Asia WGS AF: 0.262 AC: 912 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	0.020
DANN	Benign	0.52

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: rs688136; hg19: chr6-153080061; COSMIC: COSV65888491;