chr3-42525981-G-A

Variant names:

• chr3-42525981-G-A
• rs17074546
• NM_004624.4:c.387G>A

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_001251883.2(VIPR1):​c.14G>A​(p.Arg5Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00303 in 1,611,760 control chromosomes in the GnomAD database, including 135 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/17 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.016 (70 hom., cov: 32)
  • Exomes 𝑓: 0.0016 (65 hom.)
• Consequence: VIPR1 NM_001251883.2 missense
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -1.57
• 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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0025151372).
• BP6: Variant 3-42525981-G-A is Benign according to our data. Variant chr3-42525981-G-A is described in ClinVar as Benign. ClinVar VariationId is 787782.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0538 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001251883.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	VIPR1	NM_004624.4	MANE Select	c.387G>A	p.Ala129Ala	synonymous	Exon 4 of 13	NP_004615.2
	VIPR1	NM_001251883.2		c.14G>A	p.Arg5Gln	missense	Exon 3 of 10	NP_001238812.1	P32241-3
	VIPR1	NM_001251885.2		c.306G>A	p.Ala102Ala	synonymous	Exon 4 of 13	NP_001238814.1	B4DNY6

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	VIPR1	ENST00000325123.5	TSL:1 MANE Select	c.387G>A	p.Ala129Ala	synonymous	Exon 4 of 13	ENSP00000327246.4	P32241-1
	VIPR1	ENST00000883021.1		c.417G>A	p.Ala139Ala	synonymous	Exon 4 of 13	ENSP00000553080.1
	VIPR1	ENST00000883016.1		c.387G>A	p.Ala129Ala	synonymous	Exon 4 of 13	ENSP00000553075.1

Frequencies

GnomAD3 genomes AF: 0.0163 AC: 2485 AN: 152204 Hom.: 70 Cov.: 32

Gnomad AFR AF: 0.0557

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00818

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000193

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.000265

Gnomad OTH AF: 0.0139

GnomAD2 exomes AF: 0.00394 AC: 963 AN: 244164 AF XY: 0.00299

Gnomad AFR exome AF: 0.0541

Gnomad AMR exome AF: 0.00247

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.000275

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000244

Gnomad OTH exome AF: 0.00151

GnomAD4 exome AF: 0.00164 AC: 2393 AN: 1459438 Hom.: 65 Cov.: 30 AF XY: 0.00138 AC XY: 1005 AN XY: 725660

African (AFR) AF: 0.0542 AC: 1812 AN: 33434

American (AMR) AF: 0.00349 AC: 155 AN: 44450

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26072

East Asian (EAS) AF: 0.000151 AC: 6 AN: 39630

South Asian (SAS) AF: 0.000164 AC: 14 AN: 85478

European-Finnish (FIN) AF: 0.0000188 AC: 1 AN: 53202

Middle Eastern (MID) AF: 0.00226 AC: 13 AN: 5762

European-Non Finnish (NFE) AF: 0.000135 AC: 150 AN: 1111090

Other (OTH) AF: 0.00401 AC: 242 AN: 60320

GnomAD4 genome AF: 0.0163 AC: 2490 AN: 152322 Hom.: 70 Cov.: 32 AF XY: 0.0160 AC XY: 1189 AN XY: 74488

African (AFR) AF: 0.0557 AC: 2316 AN: 41572

American (AMR) AF: 0.00810 AC: 124 AN: 15304

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.000193 AC: 1 AN: 5172

South Asian (SAS) AF: 0.000207 AC: 1 AN: 4826

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10624

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

European-Non Finnish (NFE) AF: 0.000265 AC: 18 AN: 68034

Other (OTH) AF: 0.0137 AC: 29 AN: 2114

Alfa AF: 0.00919 Hom.: 14

Bravo AF: 0.0182

TwinsUK AF: 0.00 AC: 0

ALSPAC AF: 0.000519 AC: 2

ESP6500AA AF: 0.0506 AC: 223

ESP6500EA AF: 0.000698 AC: 6

ExAC AF: 0.00487 AC: 591

Asia WGS AF: 0.00404 AC: 14 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.12
BayesDel_addAF	Benign	-0.46	T
BayesDel_noAF	Benign	-0.40
CADD	Benign	0.086
DANN	Uncertain	0.99
Eigen	Benign	-1.0
Eigen_PC	Benign	-1.1
FATHMM_MKL	Benign	0.0029	N
LIST_S2	Benign	0.43	T
MetaRNN	Benign	0.0025	T
MetaSVM	Benign	-1.0	T
PhyloP100		-1.6
PROVEAN	Benign	0.69	N
REVEL	Benign	0.086
Sift	Benign	0.94	T
Vest4		0.11
MVP		0.12
ClinPred		0.0087	T
GERP RS		-2.8
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: rs17074546; hg19: chr3-42567473;