Variant chr2-26134940-C-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_ModerateBP6_ModerateBP7BS1BS2

The NM_016131.5(RAB10):c.522C>A(p.Thr174=) variant causes a splice region, synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00177 in 1,611,276 control chromosomes in the GnomAD database, including 36 homozygotes. In-silico tool predicts a benign outcome for this variant. 1/1 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.0086 ( 26 hom., cov: 33)

Exomes 𝑓: 0.0011 ( 10 hom. )

Consequence

RAB10
NM_016131.5 splice_region, synonymous

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 2.17

Variant links:

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]

RAB10 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -13 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.43).

BP6

Variant 2-26134940-C-A is Benign according to our data. Variant chr2-26134940-C-A is described in ClinVar as [Benign]. Clinvar id is 714110.Status of the report is criteria_provided_single_submitter, 1 stars.

BP7

Synonymous conserved (PhyloP=2.17 with no splicing effect.

BS1

Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.0086 (1307/152054) while in subpopulation AFR AF= 0.028 (1162/41460). AF 95% confidence interval is 0.0267. There are 26 homozygotes in gnomad4. There are 617 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.

BS2

High AC in GnomAd4 at 1307 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
RAB10	NM_016131.5 linkuse as main transcript	c.522C>A	p.Thr174=	splice_region_variant, synonymous_variant	6/6	ENST00000264710.5
RAB10	XM_047443004.1 linkuse as main transcript	c.507C>A	p.Thr169=	splice_region_variant, synonymous_variant	6/6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris
RAB10	ENST00000264710.5 linkuse as main transcript	c.522C>A	p.Thr174=	splice_region_variant, synonymous_variant	6/6	1	NM_016131.5	P1
RAB10	ENST00000462003.5 linkuse as main transcript	n.488C>A		splice_region_variant, non_coding_transcript_exon_variant	6/6	4
RAB10	ENST00000473035.1 linkuse as main transcript	n.443C>A		splice_region_variant, non_coding_transcript_exon_variant	6/6	4
RAB10	ENST00000495146.5 linkuse as main transcript	n.885C>A		splice_region_variant, non_coding_transcript_exon_variant	5/5	5

Frequencies

GnomAD3 genomes

AF:

0.00862

AC:

1309

AN:

151936

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0282

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00551

Gnomad ASJ

AF:

0.00144

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.0158

Gnomad NFE

AF:

0.000485

Gnomad OTH

AF:

0.00863

GnomAD3 exomes

AF:

0.00268

AC:

671

AN:

250222

Hom.:

AF XY:

0.00208

AC XY:

281

AN XY:

135264

show subpopulations

Gnomad AFR exome

AF:

0.0288

Gnomad AMR exome

AF:

0.00330

Gnomad ASJ exome

AF:

0.00149

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000657

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000503

Gnomad OTH exome

AF:

0.00296

GnomAD4 exome

AF:

0.00105

AC:

1537

AN:

1459222

Hom.:

Cov.:

AF XY:

0.000990

AC XY:

719

AN XY:

726068

show subpopulations

Gnomad4 AFR exome

AF:

0.0255

Gnomad4 AMR exome

AF:

0.00364

Gnomad4 ASJ exome

AF:

0.00172

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000581

Gnomad4 FIN exome

AF:

0.0000375

Gnomad4 NFE exome

AF:

0.000268

Gnomad4 OTH exome

AF:

0.00252

GnomAD4 genome

AF:

0.00860

AC:

1307

AN:

152054

Hom.:

Cov.:

AF XY:

0.00830

AC XY:

617

AN XY:

74324

show subpopulations

Gnomad4 AFR

AF:

0.0280

Gnomad4 AMR

AF:

0.00550

Gnomad4 ASJ

AF:

0.00144

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000485

Gnomad4 OTH

AF:

0.00854

Alfa

AF:

0.00380

Hom.:

Bravo

AF:

0.00924

Asia WGS

AF:

0.00115

AC:

AN:

3478

EpiCase

AF:

0.000328

EpiControl

AF:

0.000416

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

May 03, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.43

CADD

Benign

DANN

Benign

0.69

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over