3-42525927-G-A

Variant names:

• chr3-42525927-G-A
• rs34664814
• NM_004624.4:c.333G>A

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BS1 BS2

The NM_004624.4(VIPR1):​c.333G>A​(p.Thr111Thr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00314 in 1,613,520 control chromosomes in the GnomAD database, including 85 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.015 (36 hom., cov: 32)
  • Exomes 𝑓: 0.0019 (49 hom.)
• Consequence: VIPR1 NM_004624.4 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -3.51
• Publications: 3 publications found

Genes affected

VIPR1 (HGNC:12694): (vasoactive intestinal peptide receptor 1) This gene encodes a receptor for vasoactive intestinal peptide, a small neuropeptide. Vasoactive intestinal peptide is involved in smooth muscle relaxation, exocrine and endocrine secretion, and water and ion flux in lung and intestinal epithelia. Its actions are effected through integral membrane receptors associated with a guanine nucleotide binding protein which activates adenylate cyclase. Several transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Oct 2011]

VIPR1-AS1 (HGNC:40610): (VIPR1 antisense RNA 1)

ACMG classification

Our verdict: Benign. The variant received -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.78).
• BP6: Variant 3-42525927-G-A is Benign according to our data. Variant chr3-42525927-G-A is described in ClinVar as [Benign]. Clinvar id is 767896.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-3.51 with no splicing effect.
• BS1: Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.0147 (2246/152322) while in subpopulation AFR AF = 0.0483 (2008/41566). AF 95% confidence interval is 0.0465. There are 36 homozygotes in GnomAd4. There are 1059 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 36 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
VIPR1	NM_004624.4	c.333G>A	p.Thr111Thr	synonymous_variant	Exon 4 of 13	ENST00000325123.5	NP_004615.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
VIPR1	ENST00000325123.5	c.333G>A	p.Thr111Thr	synonymous_variant	Exon 4 of 13	1	NM_004624.4	ENSP00000327246.4

Frequencies

GnomAD3 genomes AF: 0.0147 AC: 2233 AN: 152204 Hom.: 35 Cov.: 32

Gnomad AFR AF: 0.0483

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00726

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.0139

Gnomad SAS AF: 0.000829

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.000250

Gnomad OTH AF: 0.0124

GnomAD2 exomes AF: 0.00464 AC: 1154 AN: 248482 AF XY: 0.00340

Gnomad AFR exome AF: 0.0463

Gnomad AMR exome AF: 0.00349

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.0128

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000302

Gnomad OTH exome AF: 0.00314

GnomAD4 exome AF: 0.00193 AC: 2823 AN: 1461198 Hom.: 49 Cov.: 31 AF XY: 0.00166 AC XY: 1208 AN XY: 726832

African (AFR) AF: 0.0475 AC: 1590 AN: 33472

American (AMR) AF: 0.00358 AC: 160 AN: 44636

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26110

East Asian (EAS) AF: 0.0157 AC: 623 AN: 39682

South Asian (SAS) AF: 0.000337 AC: 29 AN: 86030

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53344

Middle Eastern (MID) AF: 0.00347 AC: 20 AN: 5760

European-Non Finnish (NFE) AF: 0.000153 AC: 170 AN: 1111796

Other (OTH) AF: 0.00383 AC: 231 AN: 60368

GnomAD4 genome AF: 0.0147 AC: 2246 AN: 152322 Hom.: 36 Cov.: 32 AF XY: 0.0142 AC XY: 1059 AN XY: 74486

African (AFR) AF: 0.0483 AC: 2008 AN: 41566

American (AMR) AF: 0.00719 AC: 110 AN: 15306

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.0139 AC: 72 AN: 5180

South Asian (SAS) AF: 0.000829 AC: 4 AN: 4824

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10622

Middle Eastern (MID) AF: 0.00340 AC: 1 AN: 294

European-Non Finnish (NFE) AF: 0.000250 AC: 17 AN: 68032

Other (OTH) AF: 0.0161 AC: 34 AN: 2114

Alfa AF: 0.00791 Hom.: 13

Bravo AF: 0.0167

Asia WGS AF: 0.00433 AC: 15 AN: 3478

EpiCase AF: 0.000491

EpiControl AF: 0.000356

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Dec 31, 2019

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

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Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.78
CADD	Benign	0.48
DANN	Benign	0.89
PhyloP100		-3.5
Mutation Taster		=99/1	polymorphism

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

Other links and lift over

dbSNP: rs34664814; hg19: chr3-42567419;