Genetic Variant NM_004218.4:c.41-94G>C (chr19-8399769-G-C) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_004218.4(RAB11B):c.41-94G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000159 in 1,260,080 control chromosomes in the GnomAD database, with no homozygous occurrence. 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 0.0 ( 0 hom., cov: 34)

Exomes 𝑓: 0.0000016 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

RAB11B
NM_004218.4 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -4.57

Publications

0 publications found

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 Gene-Disease associations (from GenCC):

neurodevelopmental disorder with ataxic gait, absent speech, and decreased cortical white matter
Inheritance: AD Classification: STRONG, MODERATE Submitted by: Labcorp Genetics (formerly Invitae), G2P, Ambry Genetics

RAB11B links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

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

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_004218.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RAB11B	NM_004218.4	MANE Select	c.41-94G>C		intron	N/A	NP_004209.2	Q15907-1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
RAB11B	ENST00000328024.11	TSL:1 MANE Select	c.41-94G>C	intron	N/A	ENSP00000333547.5	Q15907-1
RAB11B	ENST00000896951.1		c.41-94G>C	intron	N/A	ENSP00000567010.1
RAB11B	ENST00000949520.1		c.41-94G>C	intron	N/A	ENSP00000619579.1

Frequencies

GnomAD3 genomes

AF:

0.00

AC:

AN:

152176

Hom.:

Cov.:

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.00000159

AC:

AN:

1260080

Hom.:

AF XY:

0.00000321

AC XY:

AN XY:

622620

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

29562

American (AMR)

AF:

0.00

AC:

AN:

37602

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

21412

East Asian (EAS)

AF:

0.00

AC:

AN:

37134

South Asian (SAS)

AF:

0.00

AC:

AN:

71976

European-Finnish (FIN)

AF:

0.00

AC:

AN:

49512

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4794

European-Non Finnish (NFE)

AF:

0.00000209

AC:

AN:

955122

Other (OTH)

AF:

0.00

AC:

AN:

52966

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.425

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Data not reliable, filtered out with message: AC0;AS_VQSR

AF:

0.00

AC:

AN:

152176

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

74334

African (AFR)

AF:

0.00

AC:

AN:

41462

American (AMR)

AF:

0.00

AC:

AN:

15284

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5192

South Asian (SAS)

AF:

0.00

AC:

AN:

4832

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10600

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

68020

Other (OTH)

AF:

0.00

AC:

AN:

2086

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.86

CADD

Benign

0.025

(source)

DANN

Benign

0.41

PhyloP100

-4.6

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over