19-8404854-C-T

Variant names:

• chr19-8404854-C-T
• rs2967605
• ENST00000949520.1:c.*21-112C>T

Variant summary

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

The ENST00000949520.1(RAB11B):​c.*21-112C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.207 in 152,128 control chromosomes in the GnomAD database, including 3,848 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 0.21 (3848 hom., cov: 32)
• Consequence: RAB11B ENST00000949520.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.334
• Publications: 59 publications found

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

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.581 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000949520.1. 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
There are no transcript annotations for this variant.

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RAB11B	ENST00000949520.1		c.*21-112C>T		intron	N/A	ENSP00000619579.1

Frequencies

GnomAD3 genomes AF: 0.207 AC: 31522 AN: 152010 Hom.: 3851 Cov.: 32

Gnomad AFR AF: 0.214

Gnomad AMI AF: 0.307

Gnomad AMR AF: 0.217

Gnomad ASJ AF: 0.103

Gnomad EAS AF: 0.599

Gnomad SAS AF: 0.285

Gnomad FIN AF: 0.141

Gnomad MID AF: 0.206

Gnomad NFE AF: 0.180

Gnomad OTH AF: 0.210

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

GnomAD4 genome AF: 0.207 AC: 31544 AN: 152128 Hom.: 3848 Cov.: 32 AF XY: 0.208 AC XY: 15485 AN XY: 74378

African (AFR) AF: 0.214 AC: 8886 AN: 41500

American (AMR) AF: 0.217 AC: 3319 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.103 AC: 356 AN: 3468

East Asian (EAS) AF: 0.599 AC: 3084 AN: 5152

South Asian (SAS) AF: 0.285 AC: 1373 AN: 4822

European-Finnish (FIN) AF: 0.141 AC: 1498 AN: 10608

Middle Eastern (MID) AF: 0.214 AC: 63 AN: 294

European-Non Finnish (NFE) AF: 0.180 AC: 12236 AN: 67982

Other (OTH) AF: 0.213 AC: 450 AN: 2114

Alfa AF: 0.196 Hom.: 12164

Bravo AF: 0.215

Asia WGS AF: 0.419 AC: 1453 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	5.0
DANN	Benign	0.65
PhyloP100		0.33

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: rs2967605; hg19: chr19-8469738;