rs548753085

Variant names:

• chr2-240629985-C-A
• NM_005301.5:c.33C>A

Your query was ambiguous. Multiple possible variants found:

• chr2-240629985-C-A
• chr2-240629985-C-T

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_005301.5(GPR35):​c.33C>A​(p.Ser11Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000687 in 1,456,308 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. S11S) has been classified as Likely benign.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 6.9e-7 (0 hom.)
• Consequence: GPR35 NM_005301.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.97

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 -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.049705356).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GPR35	NM_005301.5	c.33C>A	p.Ser11Arg	missense_variant	Exon 2 of 2	ENST00000407714.2	NP_005292.2
GPR35	NM_001195381.3	c.126C>A	p.Ser42Arg	missense_variant	Exon 6 of 6		NP_001182310.1
GPR35	NM_001195382.3	c.126C>A	p.Ser42Arg	missense_variant	Exon 6 of 6		NP_001182311.1
GPR35	NM_001394730.1	c.126C>A	p.Ser42Arg	missense_variant	Exon 6 of 6		NP_001381659.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GPR35	ENST00000407714.2	c.33C>A	p.Ser11Arg	missense_variant	Exon 2 of 2	1	NM_005301.5	ENSP00000384263.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 6.87e-7 AC: 1 AN: 1456308 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 723520

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 9.02e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.20
BayesDel_addAF	Benign	-0.32	T
BayesDel_noAF	Benign	-0.69
CADD	Benign	0.094
DANN	Benign	0.87
DEOGEN2	Benign	0.020	T;T;.;T;T
Eigen	Benign	-2.2
Eigen_PC	Benign	-2.3
FATHMM_MKL	Benign	0.028	N
LIST_S2	Benign	0.30	.;.;T;.;T
M_CAP	Benign	0.0010	T
MetaRNN	Benign	0.050	T;T;T;T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.55	N;N;.;N;N
PrimateAI	Benign	0.32	T
PROVEAN	Benign	-1.5	N;N;.;N;.
REVEL	Benign	0.026
Sift	Benign	0.079	T;T;.;T;.
Sift4G	Benign	0.46	T;T;T;T;T
Polyphen		0.0	B;B;.;B;B
Vest4		0.15
MutPred		0.35		Loss of glycosylation at S11 (P = 0.0217);Loss of glycosylation at S11 (P = 0.0217);.;Loss of glycosylation at S11 (P = 0.0217);Loss of glycosylation at S11 (P = 0.0217);
MVP		0.12
MPC		0.31
ClinPred		0.075	T
GERP RS		-4.3
Varity_R		0.085
gMVP		0.067

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr2-241569402;