Genetic Variant RAB11B:c.41-94G>A (chr19-8399769-G-A) – ACMG Classification: Benign (-20 pts)

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_004218.4(RAB11B):c.41-94G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.292 in 1,410,438 control chromosomes in the GnomAD database, including 62,533 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.25 ( 5341 hom., cov: 34)

Exomes 𝑓: 0.30 ( 57192 hom. )

Consequence

RAB11B
NM_004218.4 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -4.57

Variant links:

Genes affected

RAB11B (HGNC:9761): (RAB11B, member RAS oncogene family) The Ras superfamily of small GTP-binding proteins, which includes the Ras (see MIM 190020), Ral (see MIM 179550), Rho (see MIM 165390), Rap (see MIM 179520), and Rab (see MIM 179508) families, is involved in controlling a diverse set of essential cellular functions. The Rab family, including RAB11B, appears to play a critical role in regulating exocytotic and endocytotic pathways (summary by Zhu et al., 1994 [PubMed 7811277]).[supplied by OMIM, Nov 2010]

RAB11B links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.86).

BP6

Variant 19-8399769-G-A is Benign according to our data. Variant chr19-8399769-G-A is described in ClinVar as [Benign]. Clinvar id is 1275947.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.305 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RAB11B	NM_004218.4 link	c.41-94G>A		intron_variant	Intron 1 of 4	ENST00000328024.11	NP_004209.2	Q15907-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RAB11B	ENST00000328024.11 link	c.41-94G>A		intron_variant	Intron 1 of 4	1	NM_004218.4	ENSP00000333547.5		Q15907-1

Frequencies

GnomAD3 genomes

AF:

0.252

AC:

38345

AN:

152140

Hom.:

5343

Cov.:

show subpopulations

Gnomad AFR

AF:

0.125

Gnomad AMI

AF:

0.257

Gnomad AMR

AF:

0.268

Gnomad ASJ

AF:

0.321

Gnomad EAS

AF:

0.276

Gnomad SAS

AF:

0.199

Gnomad FIN

AF:

0.354

Gnomad MID

AF:

0.313

Gnomad NFE

AF:

0.308

Gnomad OTH

AF:

0.246

GnomAD4 exome

AF:

0.297

AC:

374012

AN:

1258180

Hom.:

57192

AF XY:

0.296

AC XY:

183826

AN XY:

621640

show subpopulations

Gnomad4 AFR exome

AF:

0.117

Gnomad4 AMR exome

AF:

0.234

Gnomad4 ASJ exome

AF:

0.320

Gnomad4 EAS exome

AF:

0.265

Gnomad4 SAS exome

AF:

0.199

Gnomad4 FIN exome

AF:

0.343

Gnomad4 NFE exome

AF:

0.312

Gnomad4 OTH exome

AF:

0.288

GnomAD4 genome

AF:

0.252

AC:

38345

AN:

152258

Hom.:

5341

Cov.:

AF XY:

0.255

AC XY:

18980

AN XY:

74442

show subpopulations

Gnomad4 AFR

AF:

0.124

Gnomad4 AMR

AF:

0.268

Gnomad4 ASJ

AF:

0.321

Gnomad4 EAS

AF:

0.276

Gnomad4 SAS

AF:

0.200

Gnomad4 FIN

AF:

0.354

Gnomad4 NFE

AF:

0.308

Gnomad4 OTH

AF:

0.244

Alfa

AF:

0.298

Hom.:

1419

Bravo

AF:

0.241

Asia WGS

AF:

0.208

AC:

726

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

May 14, 2021

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.86

CADD

Benign

0.043

DANN

Benign

0.47

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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