chr2-240624322-G-A

Position:

• chr2-240624322-G-A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001195381.3(GPR35):​c.89+5291G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.258 in 152,026 control chromosomes in the GnomAD database, including 5,465 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 0.26 (5465 hom., cov: 32)
• Consequence: GPR35 NM_001195381.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -3.41

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 Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.94).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.348 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GPR35	NM_001195381.3	c.89+5291G>A		intron_variant			NP_001182310.1
GPR35	NM_001195382.3	c.89+5291G>A		intron_variant			NP_001182311.1
GPR35	NM_001394730.1	c.89+5291G>A		intron_variant			NP_001381659.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GPR35	ENST00000319838.10	c.-5+5291G>A		intron_variant		2		ENSP00000322731	P2
GPR35	ENST00000403859.1	c.-5+5291G>A		intron_variant		2		ENSP00000385140	P2
GPR35	ENST00000430267.2	c.89+5291G>A		intron_variant		5		ENSP00000411788	A2

Frequencies

GnomAD3 genomes AF: 0.258 AC: 39210 AN: 151908 Hom.: 5449 Cov.: 32

Gnomad AFR AF: 0.329

Gnomad AMI AF: 0.270

Gnomad AMR AF: 0.355

Gnomad ASJ AF: 0.123

Gnomad EAS AF: 0.302

Gnomad SAS AF: 0.151

Gnomad FIN AF: 0.280

Gnomad MID AF: 0.146

Gnomad NFE AF: 0.202

Gnomad OTH AF: 0.230

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

GnomAD4 genome AF: 0.258 AC: 39255 AN: 152026 Hom.: 5465 Cov.: 32 AF XY: 0.260 AC XY: 19323 AN XY: 74308

Gnomad4 AFR AF: 0.329

Gnomad4 AMR AF: 0.356

Gnomad4 ASJ AF: 0.123

Gnomad4 EAS AF: 0.301

Gnomad4 SAS AF: 0.151

Gnomad4 FIN AF: 0.280

Gnomad4 NFE AF: 0.202

Gnomad4 OTH AF: 0.228

Alfa AF: 0.204 Hom.: 4204

Bravo AF: 0.270

Asia WGS AF: 0.224 AC: 779 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	4.5
DANN	Benign	0.56

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: rs4676410; hg19: chr2-241563739;