rs4676411

Variant names:

• chr2-240621671-G-A
• rs4676411
• NM_001195381.3:c.89+2640G>A

Your query was ambiguous. Multiple possible variants found:

• chr2-240621671-G-A
• chr2-240621671-G-C
• chr2-240621671-G-T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001195381.3(GPR35):​c.89+2640G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000329 in 151,946 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.000033 (0 hom., cov: 33)
• Consequence: GPR35 NM_001195381.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.671
• Publications: 19 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.98).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GPR35	NM_001195381.3	c.89+2640G>A		intron_variant	Intron 5 of 5		NP_001182310.1
GPR35	NM_001195382.3	c.89+2640G>A		intron_variant	Intron 5 of 5		NP_001182311.1
GPR35	NM_001394730.1	c.89+2640G>A		intron_variant	Intron 5 of 5		NP_001381659.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GPR35	ENST00000430267.2	c.89+2640G>A		intron_variant	Intron 1 of 1	5		ENSP00000411788.2
GPR35	ENST00000319838.10	c.-5+2640G>A		intron_variant	Intron 5 of 5	2		ENSP00000322731.5
GPR35	ENST00000403859.1	c.-5+2640G>A		intron_variant	Intron 5 of 5	2		ENSP00000385140.1

Frequencies

GnomAD3 genomes AF: 0.0000329 AC: 5 AN: 151946 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.0000968

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000147

Gnomad OTH AF: 0.00

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.0000329 AC: 5 AN: 151946 Hom.: 0 Cov.: 33 AF XY: 0.0000269 AC XY: 2 AN XY: 74216

African (AFR) AF: 0.0000968 AC: 4 AN: 41324

American (AMR) AF: 0.00 AC: 0 AN: 15262

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

East Asian (EAS) AF: 0.00 AC: 0 AN: 5194

South Asian (SAS) AF: 0.00 AC: 0 AN: 4828

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10538

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.0000147 AC: 1 AN: 68008

Other (OTH) AF: 0.00 AC: 0 AN: 2094

Alfa AF: 0.00 Hom.: 12818

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	2.3
DANN	Benign	0.94
PhyloP100		-0.67

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: rs4676411; hg19: chr2-241561088;