19-8390428-G-A

Variant names:

• chr19-8390428-G-A
• rs2913976
• NM_004218.4:c.12G>A

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4 BP6_Very_Strong BP7 BS2

The NM_004218.4(RAB11B):​c.12G>A​(p.Arg4Arg) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00752 in 1,526,692 control chromosomes in the GnomAD database, including 65 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★). Synonymous variant affecting the same amino acid position (i.e. R4R) has been classified as Likely benign.

• Frequency:
  • Genomes: 𝑓 0.0056 (2 hom., cov: 32)
  • Exomes 𝑓: 0.0077 (63 hom.)
• Consequence: RAB11B NM_004218.4 synonymous
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: 1.18
• Publications: 3 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-AS1 (HGNC:44178): (RAB11B antisense RNA 1)

ACMG classification

Our verdict: Benign. The variant received -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.15).
• BP6: Variant 19-8390428-G-A is Benign according to our data. Variant chr19-8390428-G-A is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 1164472.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=1.17 with no splicing effect.
• BS2: High AC in GnomAd4 at 849 AD gene.

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.12G>A	p.Arg4Arg	synonymous	Exon 1 of 5	NP_004209.2	Q15907-1
	RAB11B-AS1	NR_038237.1		n.264C>T		non_coding_transcript_exon	Exon 1 of 3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RAB11B	ENST00000328024.11	TSL:1 MANE Select	c.12G>A	p.Arg4Arg	synonymous	Exon 1 of 5	ENSP00000333547.5	Q15907-1
	RAB11B-AS1	ENST00000593581.7	TSL:1	n.258C>T		non_coding_transcript_exon	Exon 1 of 3
	RAB11B	ENST00000896951.1		c.12G>A	p.Arg4Arg	synonymous	Exon 1 of 5	ENSP00000567010.1

Frequencies

GnomAD3 genomes AF: 0.00558 AC: 849 AN: 152264 Hom.: 2 Cov.: 32

Gnomad AFR AF: 0.00162

Gnomad AMI AF: 0.0197

Gnomad AMR AF: 0.00504

Gnomad ASJ AF: 0.00173

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000620

Gnomad FIN AF: 0.00932

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00830

Gnomad OTH AF: 0.00669

GnomAD2 exomes AF: 0.00553 AC: 957 AN: 172950 AF XY: 0.00556

Gnomad AFR exome AF: 0.00212

Gnomad AMR exome AF: 0.00246

Gnomad ASJ exome AF: 0.00202

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00673

Gnomad NFE exome AF: 0.00854

Gnomad OTH exome AF: 0.00610

GnomAD4 exome AF: 0.00773 AC: 10629 AN: 1374310 Hom.: 63 Cov.: 30 AF XY: 0.00760 AC XY: 5190 AN XY: 682912

African (AFR) AF: 0.00113 AC: 31 AN: 27520

American (AMR) AF: 0.00346 AC: 97 AN: 28046

Ashkenazi Jewish (ASJ) AF: 0.00276 AC: 64 AN: 23172

East Asian (EAS) AF: 0.00 AC: 0 AN: 31980

South Asian (SAS) AF: 0.000522 AC: 40 AN: 76670

European-Finnish (FIN) AF: 0.00754 AC: 389 AN: 51580

Middle Eastern (MID) AF: 0.000908 AC: 5 AN: 5506

European-Non Finnish (NFE) AF: 0.00894 AC: 9601 AN: 1073528

Other (OTH) AF: 0.00714 AC: 402 AN: 56308

GnomAD4 genome AF: 0.00557 AC: 849 AN: 152382 Hom.: 2 Cov.: 32 AF XY: 0.00534 AC XY: 398 AN XY: 74520

African (AFR) AF: 0.00161 AC: 67 AN: 41588

American (AMR) AF: 0.00503 AC: 77 AN: 15310

Ashkenazi Jewish (ASJ) AF: 0.00173 AC: 6 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5190

South Asian (SAS) AF: 0.000621 AC: 3 AN: 4834

European-Finnish (FIN) AF: 0.00932 AC: 99 AN: 10628

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.00830 AC: 565 AN: 68040

Other (OTH) AF: 0.00662 AC: 14 AN: 2114

Alfa AF: 0.00673 Hom.: 2

Bravo AF: 0.00518

Asia WGS AF: 0.000577 AC: 2 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign/Likely benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	3	not provided (3)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.15
CADD	Benign	20
DANN	Benign	0.96
PhyloP100		1.2
PromoterAI		0.087	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.9
Mutation Taster		=90/10	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		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: rs2913976; hg19: chr19-8455312;