3-42511624-A-G

Variant names:

• chr3-42511624-A-G
• rs421558
• NM_004624.4:c.79-2125A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_004624.4(VIPR1):​c.79-2125A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.809 in 151,886 control chromosomes in the GnomAD database, including 49,810 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 0.81 (49789 hom., cov: 32)
  • Exomes 𝑓: 0.90 (21 hom.)
• Consequence: VIPR1 NM_004624.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.11
• Publications: 2 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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.94).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.963 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_004624.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	VIPR1	NM_004624.4	MANE Select	c.79-2125A>G		intron	N/A	NP_004615.2
	VIPR1	NM_001251885.2		c.15-2142A>G		intron	N/A	NP_001238814.1
	VIPR1	NM_001251882.2		c.-244-1127A>G		intron	N/A	NP_001238811.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	VIPR1	ENST00000325123.5	TSL:1 MANE Select	c.79-2125A>G		intron	N/A	ENSP00000327246.4
	VIPR1	ENST00000433647.5	TSL:2	c.-244-1127A>G		intron	N/A	ENSP00000394950.1
	VIPR1	ENST00000543411.5	TSL:2	c.44-7599A>G		intron	N/A	ENSP00000445701.1

Frequencies

GnomAD3 genomes AF: 0.809 AC: 122749 AN: 151714 Hom.: 49740 Cov.: 32

Gnomad AFR AF: 0.825

Gnomad AMI AF: 0.773

Gnomad AMR AF: 0.862

Gnomad ASJ AF: 0.812

Gnomad EAS AF: 0.986

Gnomad SAS AF: 0.839

Gnomad FIN AF: 0.751

Gnomad MID AF: 0.796

Gnomad NFE AF: 0.780

Gnomad OTH AF: 0.833

GnomAD4 exome AF: 0.904 AC: 47 AN: 52 Hom.: 21 AF XY: 0.875 AC XY: 28 AN XY: 32

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AF: 1.00 AC: 2 AN: 2

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AF: 0.875 AC: 7 AN: 8

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.933 AC: 28 AN: 30

Other (OTH) AF: 0.833 AC: 10 AN: 12

GnomAD4 genome AF: 0.809 AC: 122857 AN: 151834 Hom.: 49789 Cov.: 32 AF XY: 0.809 AC XY: 60051 AN XY: 74208

African (AFR) AF: 0.825 AC: 34139 AN: 41358

American (AMR) AF: 0.862 AC: 13166 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.812 AC: 2818 AN: 3472

East Asian (EAS) AF: 0.985 AC: 5094 AN: 5170

South Asian (SAS) AF: 0.839 AC: 4044 AN: 4820

European-Finnish (FIN) AF: 0.751 AC: 7922 AN: 10546

Middle Eastern (MID) AF: 0.795 AC: 232 AN: 292

European-Non Finnish (NFE) AF: 0.780 AC: 52978 AN: 67880

Other (OTH) AF: 0.834 AC: 1762 AN: 2112

Alfa AF: 0.789 Hom.: 6749

Bravo AF: 0.822

Asia WGS AF: 0.914 AC: 3180 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	0.84
DANN	Benign	0.58
PhyloP100		-1.1
Mutation Taster		=100/0	polymorphism (auto)

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: rs421558; hg19: chr3-42553116;