NM_004218.4:c.41-94G>A

Variant names:

• chr19-8399769-G-A
• rs2913970
• NM_004218.4:c.41-94G>A

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

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
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -4.57
• Publications: 6 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 -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 VariationId 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.

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>A		intron	N/A	NP_004209.2	Q15907-1

Ensembl Transcripts

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

Frequencies

GnomAD3 genomes AF: 0.252 AC: 38345 AN: 152140 Hom.: 5343 Cov.: 34

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

African (AFR) AF: 0.117 AC: 3451 AN: 29552

American (AMR) AF: 0.234 AC: 8793 AN: 37554

Ashkenazi Jewish (ASJ) AF: 0.320 AC: 6842 AN: 21396

East Asian (EAS) AF: 0.265 AC: 9813 AN: 37098

South Asian (SAS) AF: 0.199 AC: 14280 AN: 71918

European-Finnish (FIN) AF: 0.343 AC: 16953 AN: 49460

Middle Eastern (MID) AF: 0.321 AC: 1539 AN: 4788

European-Non Finnish (NFE) AF: 0.312 AC: 297098 AN: 953522

Other (OTH) AF: 0.288 AC: 15243 AN: 52892

GnomAD4 genome AF: 0.252 AC: 38345 AN: 152258 Hom.: 5341 Cov.: 34 AF XY: 0.255 AC XY: 18980 AN XY: 74442

African (AFR) AF: 0.124 AC: 5169 AN: 41572

American (AMR) AF: 0.268 AC: 4105 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.321 AC: 1113 AN: 3470

East Asian (EAS) AF: 0.276 AC: 1426 AN: 5176

South Asian (SAS) AF: 0.200 AC: 964 AN: 4828

European-Finnish (FIN) AF: 0.354 AC: 3749 AN: 10598

Middle Eastern (MID) AF: 0.316 AC: 93 AN: 294

European-Non Finnish (NFE) AF: 0.308 AC: 20977 AN: 68004

Other (OTH) AF: 0.244 AC: 515 AN: 2108

Alfa AF: 0.294 Hom.: 1425

Bravo AF: 0.241

Asia WGS AF: 0.208 AC: 726 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	0.043
DANN	Benign	0.47
PhyloP100		-4.6
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs2913970; hg19: chr19-8464653; COSMIC: COSV60085188;