chr19-8390446-C-T

Variant names:

• chr19-8390446-C-T
• rs1971338137
• NM_004218.4:c.30C>T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4 BP6_Moderate BP7

The NM_004218.4(RAB11B):​c.30C>T​(p.Tyr10Tyr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000147 in 1,360,980 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000015 (0 hom.)
• Consequence: RAB11B NM_004218.4 synonymous
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.0460
• Publications: 0 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: 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=-0.14).
• BP6: Variant 19-8390446-C-T is Benign according to our data. Variant chr19-8390446-C-T is described in ClinVar as Likely_benign. ClinVar VariationId is 2964644.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=0.046 with no splicing effect.

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.30C>T	p.Tyr10Tyr	synonymous	Exon 1 of 5	NP_004209.2	Q15907-1
	RAB11B-AS1	NR_038237.1		n.246G>A		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.30C>T	p.Tyr10Tyr	synonymous	Exon 1 of 5	ENSP00000333547.5	Q15907-1
	RAB11B-AS1	ENST00000593581.7	TSL:1	n.240G>A		non_coding_transcript_exon	Exon 1 of 3
	RAB11B	ENST00000896951.1		c.30C>T	p.Tyr10Tyr	synonymous	Exon 1 of 5	ENSP00000567010.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000147 AC: 2 AN: 1360980 Hom.: 0 Cov.: 30 AF XY: 0.00000148 AC XY: 1 AN XY: 676052

African (AFR) AF: 0.00 AC: 0 AN: 26906

American (AMR) AF: 0.00 AC: 0 AN: 24600

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 22350

East Asian (EAS) AF: 0.00 AC: 0 AN: 31842

South Asian (SAS) AF: 0.00 AC: 0 AN: 74282

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 51250

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5442

European-Non Finnish (NFE) AF: 0.00000187 AC: 2 AN: 1068622

Other (OTH) AF: 0.00 AC: 0 AN: 55686

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.14
CADD	Benign	19
DANN	Benign	0.96
PhyloP100		0.046
PromoterAI		-0.077	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.9

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: rs1971338137; hg19: chr19-8455330;