rs10933620

Variant names:

• chr2-240610429-A-G
• rs10933620
• NM_001195381.3:c.-484+3817A>G

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 10 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]

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]

CAPN10 Gene-Disease associations (from GenCC):

• neurodevelopmental disorder

  Inheritance: AR Classification: LIMITED Submitted by: G2P

ACMG classification

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
GPR35	NM_001195381.3	c.-484+3817A>G		intron_variant	Intron 2 of 5		NP_001182310.1
GPR35	NM_001195382.3	c.-370+3817A>G		intron_variant	Intron 2 of 5		NP_001182311.1
GPR35	NM_001394730.1	c.-598+3817A>G		intron_variant	Intron 2 of 5		NP_001381659.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GPR35	ENST00000319838.10	c.-577+3817A>G		intron_variant	Intron 2 of 5	2		ENSP00000322731.5
GPR35	ENST00000403859.1	c.-463+3817A>G		intron_variant	Intron 2 of 5	2		ENSP00000385140.1
CAPN10	ENST00000270364.11	c.274-5959A>G		intron_variant	Intron 2 of 3	2		ENSP00000270364.7

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

African (AFR) AF: 0.426 AC: 17657 AN: 41418

American (AMR) AF: 0.592 AC: 9035 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.607 AC: 2105 AN: 3466

East Asian (EAS) AF: 0.664 AC: 3429 AN: 5166

South Asian (SAS) AF: 0.577 AC: 2775 AN: 4810

European-Finnish (FIN) AF: 0.552 AC: 5805 AN: 10522

Middle Eastern (MID) AF: 0.558 AC: 164 AN: 294

European-Non Finnish (NFE) AF: 0.613 AC: 41643 AN: 67976

Other (OTH) AF: 0.575 AC: 1214 AN: 2110

Alfa AF: 0.600 Hom.: 19279

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
PhyloP100		0.18
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: rs10933620; hg19: chr2-241549846;