NM_001195381.3:c.89+2640G>T

Variant names:

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

Variant summary

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

The NM_001195381.3(GPR35):​c.89+2640G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.347 in 151,988 control chromosomes in the GnomAD database, including 9,371 homozygotes. 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 0.35 (9371 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: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.01).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.434 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001195381.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GPR35	NM_001195381.3		c.89+2640G>T		intron	N/A	NP_001182310.1
	GPR35	NM_001195382.3		c.89+2640G>T		intron	N/A	NP_001182311.1
	GPR35	NM_001394730.1		c.89+2640G>T		intron	N/A	NP_001381659.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GPR35	ENST00000430267.2	TSL:5	c.89+2640G>T		intron	N/A	ENSP00000411788.2
	GPR35	ENST00000319838.10	TSL:2	c.-5+2640G>T		intron	N/A	ENSP00000322731.5
	GPR35	ENST00000403859.1	TSL:2	c.-5+2640G>T		intron	N/A	ENSP00000385140.1

Frequencies

GnomAD3 genomes AF: 0.347 AC: 52733 AN: 151872 Hom.: 9361 Cov.: 33

Gnomad AFR AF: 0.280

Gnomad AMI AF: 0.390

Gnomad AMR AF: 0.348

Gnomad ASJ AF: 0.386

Gnomad EAS AF: 0.448

Gnomad SAS AF: 0.362

Gnomad FIN AF: 0.390

Gnomad MID AF: 0.288

Gnomad NFE AF: 0.371

Gnomad OTH AF: 0.335

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

GnomAD4 genome AF: 0.347 AC: 52771 AN: 151988 Hom.: 9371 Cov.: 33 AF XY: 0.348 AC XY: 25834 AN XY: 74314

African (AFR) AF: 0.279 AC: 11569 AN: 41410

American (AMR) AF: 0.349 AC: 5331 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.386 AC: 1337 AN: 3468

East Asian (EAS) AF: 0.449 AC: 2325 AN: 5180

South Asian (SAS) AF: 0.364 AC: 1751 AN: 4816

European-Finnish (FIN) AF: 0.390 AC: 4108 AN: 10538

Middle Eastern (MID) AF: 0.279 AC: 82 AN: 294

European-Non Finnish (NFE) AF: 0.371 AC: 25204 AN: 67978

Other (OTH) AF: 0.335 AC: 708 AN: 2116

Alfa AF: 0.349 Hom.: 12818

Bravo AF: 0.346

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.78
DANN	Benign	0.24
PhyloP100		-0.67
Mutation Taster		=100/0	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: rs4676411; hg19: chr2-241561088;