rs10933620

Positions:

• chr2-240610429-A-G

Variant summary

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

The NM_001195381.3(GPR35):​c.-484+3817A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.556 in 151,942 control chromosomes in the GnomAD database, including 24,041 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 0.56 (24041 hom., cov: 31)
• Consequence: GPR35 NM_001195381.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.178

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]

CAPN10 (HGNC:1477): (calpain 10) Calpains represent a ubiquitous, well-conserved family of calcium-dependent cysteine proteases. The calpain proteins are heterodimers consisting of an invariant small subunit and variable large subunits. The large catalytic subunit has four domains: domain I, the N-terminal regulatory domain that is processed upon calpain activation; domain II, the protease domain; domain III, a linker domain of unknown function; and domain IV, the calmodulin-like calcium-binding domain. This gene encodes a large subunit. It is an atypical calpain in that it lacks the calmodulin-like calcium-binding domain and instead has a divergent C-terminal domain. It is similar in organization to calpains 5 and 6. This gene is associated with type 2 or non-insulin-dependent diabetes mellitus (NIDDM), and is located within the NIDDM1 region. Multiple alternative transcript variants have been described for this gene. [provided by RefSeq, Sep 2010]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.96).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.645 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GPR35	NM_001195381.3	c.-484+3817A>G		intron_variant			NP_001182310.1
GPR35	NM_001195382.3	c.-370+3817A>G		intron_variant			NP_001182311.1
GPR35	NM_001394730.1	c.-598+3817A>G		intron_variant			NP_001381659.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CAPN10	ENST00000270364.11	c.274-5959A>G		intron_variant		2		ENSP00000270364
GPR35	ENST00000319838.10	c.-577+3817A>G		intron_variant		2		ENSP00000322731	P2
GPR35	ENST00000403859.1	c.-463+3817A>G		intron_variant		2		ENSP00000385140	P2

Frequencies

GnomAD3 genomes AF: 0.556 AC: 84432 AN: 151824 Hom.: 24025 Cov.: 31

Gnomad AFR AF: 0.427

Gnomad AMI AF: 0.719

Gnomad AMR AF: 0.591

Gnomad ASJ AF: 0.607

Gnomad EAS AF: 0.663

Gnomad SAS AF: 0.577

Gnomad FIN AF: 0.552

Gnomad MID AF: 0.560

Gnomad NFE AF: 0.613

Gnomad OTH AF: 0.573

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

GnomAD4 genome AF: 0.556 AC: 84481 AN: 151942 Hom.: 24041 Cov.: 31 AF XY: 0.554 AC XY: 41176 AN XY: 74266

Gnomad4 AFR AF: 0.426

Gnomad4 AMR AF: 0.592

Gnomad4 ASJ AF: 0.607

Gnomad4 EAS AF: 0.664

Gnomad4 SAS AF: 0.577

Gnomad4 FIN AF: 0.552

Gnomad4 NFE AF: 0.613

Gnomad4 OTH AF: 0.575

Alfa AF: 0.600 Hom.: 14719

Bravo AF: 0.555

Asia WGS AF: 0.615 AC: 2136 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	4.3
DANN	Benign	0.31

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: rs10933620; hg19: chr2-241549846;