2-26121918-G-A

Variant names:

• chr2-26121918-G-A
• rs11126375
• NM_016131.5:c.328-5226G>A

Variant summary

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

The NM_016131.5(RAB10):​c.328-5226G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.767 in 152,106 control chromosomes in the GnomAD database, including 44,761 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 0.77 (44761 hom., cov: 31)
• Consequence: RAB10 NM_016131.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.86
• Publications: 2 publications found

Genes affected

RAB10 (HGNC:9759): (RAB10, member RAS oncogene family) RAB10 belongs to the RAS (see HRAS; MIM 190020) superfamily of small GTPases. RAB proteins localize to exocytic and endocytic compartments and regulate intracellular vesicle trafficking (Bao et al., 1998 [PubMed 9918381]).[supplied by OMIM, Mar 2009]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.05).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.85 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RAB10	NM_016131.5	c.328-5226G>A		intron_variant	Intron 3 of 5	ENST00000264710.5	NP_057215.3
RAB10	XM_047443004.1	c.313-5226G>A		intron_variant	Intron 3 of 5		XP_047298960.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RAB10	ENST00000264710.5	c.328-5226G>A		intron_variant	Intron 3 of 5	1	NM_016131.5	ENSP00000264710.4
RAB10	ENST00000462003.5	n.249-5226G>A		intron_variant	Intron 3 of 5	4
RAB10	ENST00000473035.1	n.249-5226G>A		intron_variant	Intron 3 of 5	4
RAB10	ENST00000495146.5	n.691-5226G>A		intron_variant	Intron 2 of 4	5

Frequencies

GnomAD3 genomes AF: 0.767 AC: 116557 AN: 151988 Hom.: 44746 Cov.: 31

Gnomad AFR AF: 0.716

Gnomad AMI AF: 0.768

Gnomad AMR AF: 0.776

Gnomad ASJ AF: 0.673

Gnomad EAS AF: 0.872

Gnomad SAS AF: 0.782

Gnomad FIN AF: 0.794

Gnomad MID AF: 0.677

Gnomad NFE AF: 0.788

Gnomad OTH AF: 0.761

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

GnomAD4 genome AF: 0.767 AC: 116615 AN: 152106 Hom.: 44761 Cov.: 31 AF XY: 0.767 AC XY: 56977 AN XY: 74328

African (AFR) AF: 0.715 AC: 29671 AN: 41484

American (AMR) AF: 0.776 AC: 11861 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.673 AC: 2336 AN: 3470

East Asian (EAS) AF: 0.871 AC: 4506 AN: 5172

South Asian (SAS) AF: 0.781 AC: 3765 AN: 4822

European-Finnish (FIN) AF: 0.794 AC: 8394 AN: 10568

Middle Eastern (MID) AF: 0.684 AC: 201 AN: 294

European-Non Finnish (NFE) AF: 0.788 AC: 53582 AN: 67996

Other (OTH) AF: 0.759 AC: 1599 AN: 2106

Alfa AF: 0.774 Hom.: 56487

Bravo AF: 0.763

Asia WGS AF: 0.777 AC: 2702 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.1
CADD	Benign	1.6
DANN	Benign	0.63
PhyloP100		-1.9
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0
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: rs11126375; hg19: chr2-26344787;