rs3749172

Variant names:

• chr2-240630832-A-C
• rs3749172
• NM_005301.5:c.880A>C

Your query was ambiguous. Multiple possible variants found:

• chr2-240630832-A-C
• chr2-240630832-A-T

Variant summary

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

The NM_005301.5(GPR35):​c.880A>C​(p.Ser294Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.565 in 1,612,842 control chromosomes in the GnomAD database, including 265,508 homozygotes. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. S294N) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.47 (19054 hom., cov: 33)
  • Exomes 𝑓: 0.57 (246454 hom.)
• Consequence: GPR35 NM_005301.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.16
• Publications: 52 publications found

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

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=1.4194889E-6).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.762 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_005301.5. 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
	GPR35	NM_005301.5	MANE Select	c.880A>C	p.Ser294Arg	missense	Exon 2 of 2	NP_005292.2
	GPR35	NM_001195381.3		c.973A>C	p.Ser325Arg	missense	Exon 6 of 6	NP_001182310.1
	GPR35	NM_001195382.3		c.973A>C	p.Ser325Arg	missense	Exon 6 of 6	NP_001182311.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GPR35	ENST00000407714.2	TSL:1 MANE Select	c.880A>C	p.Ser294Arg	missense	Exon 2 of 2	ENSP00000384263.1
	GPR35	ENST00000430267.2	TSL:5	c.973A>C	p.Ser325Arg	missense	Exon 2 of 2	ENSP00000411788.2
	GPR35	ENST00000319838.10	TSL:2	c.880A>C	p.Ser294Arg	missense	Exon 6 of 6	ENSP00000322731.5

Frequencies

GnomAD3 genomes AF: 0.475 AC: 72152 AN: 151968 Hom.: 19036 Cov.: 33

Gnomad AFR AF: 0.248

Gnomad AMI AF: 0.536

Gnomad AMR AF: 0.395

Gnomad ASJ AF: 0.486

Gnomad EAS AF: 0.699

Gnomad SAS AF: 0.783

Gnomad FIN AF: 0.584

Gnomad MID AF: 0.509

Gnomad NFE AF: 0.573

Gnomad OTH AF: 0.481

GnomAD2 exomes AF: 0.555 AC: 139371 AN: 250952 AF XY: 0.578

Gnomad AFR exome AF: 0.241

Gnomad AMR exome AF: 0.394

Gnomad ASJ exome AF: 0.481

Gnomad EAS exome AF: 0.703

Gnomad FIN exome AF: 0.586

Gnomad NFE exome AF: 0.567

Gnomad OTH exome AF: 0.537

GnomAD4 exome AF: 0.574 AC: 838815 AN: 1460756 Hom.: 246454 Cov.: 66 AF XY: 0.582 AC XY: 423113 AN XY: 726690

African (AFR) AF: 0.246 AC: 8226 AN: 33480

American (AMR) AF: 0.391 AC: 17502 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.483 AC: 12633 AN: 26132

East Asian (EAS) AF: 0.711 AC: 28235 AN: 39698

South Asian (SAS) AF: 0.776 AC: 66944 AN: 86256

European-Finnish (FIN) AF: 0.585 AC: 30622 AN: 52374

Middle Eastern (MID) AF: 0.531 AC: 3061 AN: 5768

European-Non Finnish (NFE) AF: 0.573 AC: 637629 AN: 1111948

Other (OTH) AF: 0.563 AC: 33963 AN: 60376

GnomAD4 genome AF: 0.475 AC: 72187 AN: 152086 Hom.: 19054 Cov.: 33 AF XY: 0.480 AC XY: 35678 AN XY: 74344

African (AFR) AF: 0.248 AC: 10286 AN: 41478

American (AMR) AF: 0.395 AC: 6037 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.486 AC: 1687 AN: 3470

East Asian (EAS) AF: 0.700 AC: 3611 AN: 5162

South Asian (SAS) AF: 0.782 AC: 3770 AN: 4818

European-Finnish (FIN) AF: 0.584 AC: 6181 AN: 10586

Middle Eastern (MID) AF: 0.514 AC: 151 AN: 294

European-Non Finnish (NFE) AF: 0.573 AC: 38953 AN: 67980

Other (OTH) AF: 0.486 AC: 1024 AN: 2106

Alfa AF: 0.534 Hom.: 48944

Bravo AF: 0.445

TwinsUK AF: 0.576 AC: 2136

ALSPAC AF: 0.589 AC: 2269

ESP6500AA AF: 0.247 AC: 1088

ESP6500EA AF: 0.565 AC: 4857

ExAC AF: 0.559 AC: 67823

Asia WGS AF: 0.712 AC: 2474 AN: 3476

EpiCase AF: 0.563

EpiControl AF: 0.562

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.13
BayesDel_addAF	Benign	-0.72	T
BayesDel_noAF	Benign	-0.66
CADD	Benign	2.3
DANN	Benign	0.22
DEOGEN2	Benign	0.0055	T
Eigen	Benign	-1.5
Eigen_PC	Benign	-1.6
FATHMM_MKL	Benign	0.026	N
LIST_S2	Benign	0.28	T
MetaRNN	Benign	0.0000014	T
MetaSVM	Benign	-0.97	T
MutationAssessor	Benign	0.20	N
PhyloP100		-1.2
PrimateAI	Benign	0.28	T
PROVEAN	Benign	1.3	N
REVEL	Benign	0.060
Sift	Benign	0.66	T
Sift4G	Benign	0.55	T
Polyphen		0.0	B
Vest4		0.045
MutPred		0.11		Loss of ubiquitination at K299 (P = 0.0283)
MPC		0.31
ClinPred		0.0013	T
GERP RS		-3.6
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.053
gMVP		0.18
Mutation Taster		=97/3	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: rs3749172; hg19: chr2-241570249; COSMIC: COSV60576322;