7-159030704-A-G

Position:

• chr7-159030704-A-G

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BS1 BS2

The NM_003382.5(VIPR2):​c.1229T>C​(p.Phe410Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00138 in 1,588,466 control chromosomes in the GnomAD database, including 17 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0062 (8 hom., cov: 33)
  • Exomes 𝑓: 0.00086 (9 hom.)
• Consequence: VIPR2 NM_003382.5 missense
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 3.29

Genes affected

VIPR2 (HGNC:12695): (vasoactive intestinal peptide receptor 2) 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. [provided by RefSeq, Aug 2011]

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0029411614).
• BP6: Variant 7-159030704-A-G is Benign according to our data. Variant chr7-159030704-A-G is described in ClinVar as [Benign]. Clinvar id is 778371.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00625 (951/152196) while in subpopulation AFR AF= 0.0211 (877/41534). AF 95% confidence interval is 0.02. There are 8 homozygotes in gnomad4. There are 436 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd4 at 8 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
VIPR2	NM_003382.5	c.1229T>C	p.Phe410Ser	missense_variant	13/13	ENST00000262178.7	NP_003373.2
VIPR2	NM_001308259.1	c.1181T>C	p.Phe394Ser	missense_variant	10/10		NP_001295188.1
VIPR2	NM_001304522.2	c.989T>C	p.Phe330Ser	missense_variant	11/11		NP_001291451.1
VIPR2	NR_130758.2	n.1659T>C		non_coding_transcript_exon_variant	13/13

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
VIPR2	ENST00000262178.7	c.1229T>C	p.Phe410Ser	missense_variant	13/13	1	NM_003382.5	ENSP00000262178.2
VIPR2	ENST00000402066.5	c.1652T>C	p.Phe551Ser	missense_variant	13/13	5		ENSP00000384497.1
VIPR2	ENST00000377633.7	c.1181T>C	p.Phe394Ser	missense_variant	10/10	2		ENSP00000366860.3

Frequencies

GnomAD3 genomes AF: 0.00625 AC: 951 AN: 152078 Hom.: 8 Cov.: 33

Gnomad AFR AF: 0.0212

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00255

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00116

Gnomad SAS AF: 0.000208

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.000250

Gnomad OTH AF: 0.00478

GnomAD3 exomes AF: 0.00183 AC: 379 AN: 206708 Hom.: 2 AF XY: 0.00150 AC XY: 168 AN XY: 112126

Gnomad AFR exome AF: 0.0219

Gnomad AMR exome AF: 0.00176

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00133

Gnomad SAS exome AF: 0.000344

Gnomad FIN exome AF: 0.0000557

Gnomad NFE exome AF: 0.000212

Gnomad OTH exome AF: 0.00116

GnomAD4 exome AF: 0.000863 AC: 1239 AN: 1436270 Hom.: 9 Cov.: 31 AF XY: 0.000781 AC XY: 556 AN XY: 712276

Gnomad4 AFR exome AF: 0.0215

Gnomad4 AMR exome AF: 0.00187

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.000571

Gnomad4 SAS exome AF: 0.000231

Gnomad4 FIN exome AF: 0.0000397

Gnomad4 NFE exome AF: 0.000278

Gnomad4 OTH exome AF: 0.00164

GnomAD4 genome AF: 0.00625 AC: 951 AN: 152196 Hom.: 8 Cov.: 33 AF XY: 0.00586 AC XY: 436 AN XY: 74402

Gnomad4 AFR AF: 0.0211

Gnomad4 AMR AF: 0.00255

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00116

Gnomad4 SAS AF: 0.000208

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000250

Gnomad4 OTH AF: 0.00473

Alfa AF: 0.00156 Hom.: 0

Bravo AF: 0.00714

ESP6500AA AF: 0.0195 AC: 85

ESP6500EA AF: 0.000467 AC: 4

ExAC AF: 0.00201 AC: 241

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Aug 28, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.086
BayesDel_addAF	Benign	-0.54	T
BayesDel_noAF	Benign	-0.53
CADD	Benign	18
DANN	Benign	0.89
DEOGEN2	Benign	0.077	T;.;T
Eigen	Benign	-1.0
Eigen_PC	Benign	-0.88
FATHMM_MKL	Benign	0.46	N
LIST_S2	Benign	0.055	T;T;T
MetaRNN	Benign	0.0029	T;T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	-0.075	N;.;.
PrimateAI	Uncertain	0.51	T
PROVEAN	Benign	-0.45	N;N;N
REVEL	Benign	0.053
Sift	Benign	0.098	T;T;T
Sift4G	Benign	0.12	T;T;T
Polyphen		0.0070	B;.;.
Vest4		0.039
MVP		0.26
MPC		0.33
ClinPred		0.0054	T
GERP RS		2.8
Varity_R		0.060
gMVP		0.35

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: rs138691820; hg19: chr7-158823395;