rs302668

Positions:

• chr11-88143743-T-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_022337.3(RAB38):​c.483+5932A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.279 in 152,116 control chromosomes in the GnomAD database, including 6,572 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 0.28 (6572 hom., cov: 32)
• Consequence: RAB38 NM_022337.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.06

Genes affected

RAB38 (HGNC:9776): (RAB38, member RAS oncogene family) Enables several functions, including AP-1 adaptor complex binding activity; AP-3 adaptor complex binding activity; and BLOC-2 complex binding activity. Involved in several processes, including endosome to melanosome transport; melanosome assembly; and phagosome acidification. Located in several cellular components, including cytoplasmic vesicle; lysosome; and mitochondria-associated endoplasmic reticulum membrane. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.329 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
RAB38	NM_022337.3	c.483+5932A>G		intron_variant		ENST00000243662.11
RAB38	XM_017017455.3	c.483+5932A>G		intron_variant
RAB38	XM_017017456.3	c.483+5932A>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RAB38	ENST00000243662.11	c.483+5932A>G		intron_variant		1	NM_022337.3	P1
RAB38	ENST00000526372.1	c.478+5932A>G		intron_variant		3
RAB38	ENST00000531138.1	c.252-29603A>G		intron_variant		2

Frequencies

GnomAD3 genomes AF: 0.279 AC: 42339 AN: 151998 Hom.: 6566 Cov.: 32

Gnomad AFR AF: 0.140

Gnomad AMI AF: 0.505

Gnomad AMR AF: 0.317

Gnomad ASJ AF: 0.303

Gnomad EAS AF: 0.303

Gnomad SAS AF: 0.258

Gnomad FIN AF: 0.376

Gnomad MID AF: 0.320

Gnomad NFE AF: 0.333

Gnomad OTH AF: 0.314

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

GnomAD4 genome AF: 0.279 AC: 42366 AN: 152116 Hom.: 6572 Cov.: 32 AF XY: 0.282 AC XY: 20960 AN XY: 74352

Gnomad4 AFR AF: 0.140

Gnomad4 AMR AF: 0.317

Gnomad4 ASJ AF: 0.303

Gnomad4 EAS AF: 0.303

Gnomad4 SAS AF: 0.259

Gnomad4 FIN AF: 0.376

Gnomad4 NFE AF: 0.333

Gnomad4 OTH AF: 0.316

Alfa AF: 0.322 Hom.: 2251

Bravo AF: 0.264

Asia WGS AF: 0.309 AC: 1080 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.055
DANN	Benign	0.48

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

LitVar

Other links and lift over

dbSNP: rs302668; hg19: chr11-87876911;