2-240630252-G-A

Variant summary

Our verdict is Likely benign. Variant got -5 ACMG points: 0P and 5B. BP4_Moderate BP6_Moderate BP7

The NM_005301.5(GPR35):c.300G>A(p.Arg100=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00299 in 1,564,452 control chromosomes in the GnomAD database, including 9 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.0024 (0 hom., cov: 33)
  • Exomes 𝑓: 0.0031 (9 hom.)
• Consequence: GPR35 NM_005301.5 synonymous
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.0510

Genes affected

GPR35 (HGNC:4492): (G protein-coupled receptor 35) Enables C-X-C chemokine receptor activity. Involved in several processes, including chemokine-mediated signaling pathway; negative regulation of voltage-gated calcium channel activity; and positive regulation of cytosolic calcium ion concentration. Is integral component of plasma membrane. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Likely_benign. Variant got -5 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.39).
• BP6: Variant 2-240630252-G-A is Benign according to our data. Variant chr2-240630252-G-A is described in ClinVar as [Benign]. Clinvar id is 791125.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=0.051 with no splicing effect.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
GPR35	NM_005301.5	c.300G>A	p.Arg100=	synonymous_variant	2/2	ENST00000407714.2
GPR35	NM_001195381.3	c.393G>A	p.Arg131=	synonymous_variant	6/6
GPR35	NM_001195382.3	c.393G>A	p.Arg131=	synonymous_variant	6/6
GPR35	NM_001394730.1	c.393G>A	p.Arg131=	synonymous_variant	6/6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GPR35	ENST00000407714.2	c.300G>A	p.Arg100=	synonymous_variant	2/2	1	NM_005301.5	P2

Frequencies

GnomAD3 genomes AF: 0.00240 AC: 365 AN: 152240 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.000651

Gnomad AMI AF: 0.0186

Gnomad AMR AF: 0.00196

Gnomad ASJ AF: 0.00576

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.000941

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00378

Gnomad OTH AF: 0.00143

GnomAD3 exomes AF: 0.00242 AC: 522 AN: 215698 Hom.: 1 AF XY: 0.00246 AC XY: 286 AN XY: 116316

Gnomad AFR exome AF: 0.000445

Gnomad AMR exome AF: 0.00256

Gnomad ASJ exome AF: 0.00532

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.0000819

Gnomad FIN exome AF: 0.00118

Gnomad NFE exome AF: 0.00354

Gnomad OTH exome AF: 0.00370

GnomAD4 exome AF: 0.00306 AC: 4315 AN: 1412094 Hom.: 9 Cov.: 34 AF XY: 0.00301 AC XY: 2099 AN XY: 697364

Gnomad4 AFR exome AF: 0.000335

Gnomad4 AMR exome AF: 0.00259

Gnomad4 ASJ exome AF: 0.00459

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000620

Gnomad4 FIN exome AF: 0.00126

Gnomad4 NFE exome AF: 0.00355

Gnomad4 OTH exome AF: 0.00251

GnomAD4 genome AF: 0.00240 AC: 365 AN: 152358 Hom.: 0 Cov.: 33 AF XY: 0.00215 AC XY: 160 AN XY: 74498

Gnomad4 AFR AF: 0.000649

Gnomad4 AMR AF: 0.00196

Gnomad4 ASJ AF: 0.00576

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000207

Gnomad4 FIN AF: 0.000941

Gnomad4 NFE AF: 0.00378

Gnomad4 OTH AF: 0.00142

Alfa AF: 0.00305 Hom.: 1

Bravo AF: 0.00236

Asia WGS AF: 0.000289 AC: 1 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Dec 31, 2019

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.39
Cadd	Benign	7.2
Dann	Benign	0.81

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: rs147336244; hg19: chr2-241569669; COSMIC: COSV100166503;