rs2239508

Positions:

• chr18-9845860-C-A
• chr18-9845860-C-G

Variant summary

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

The NM_006868.4(RAB31):​c.490+169C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.345 in 152,048 control chromosomes in the GnomAD database, including 10,731 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 0.34 (10731 hom., cov: 33)
• Consequence: RAB31 NM_006868.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.616

Genes affected

RAB31 (HGNC:9771): (RAB31, member RAS oncogene family) Enables GDP binding activity and GTP binding activity. Involved in several processes, including Golgi to plasma membrane protein transport; cellular response to insulin stimulus; and receptor internalization. Located in early endosome; phagocytic vesicle; and trans-Golgi network membrane. Biomarker of severe acute respiratory syndrome. [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=-0.86).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.563 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
RAB31	NM_006868.4	c.490+169C>A		intron_variant		ENST00000578921.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RAB31	ENST00000578921.6	c.490+169C>A		intron_variant		1	NM_006868.4	P1

Frequencies

GnomAD3 genomes AF: 0.345 AC: 52407 AN: 151930 Hom.: 10735 Cov.: 33

Gnomad AFR AF: 0.111

Gnomad AMI AF: 0.427

Gnomad AMR AF: 0.447

Gnomad ASJ AF: 0.302

Gnomad EAS AF: 0.581

Gnomad SAS AF: 0.442

Gnomad FIN AF: 0.454

Gnomad MID AF: 0.263

Gnomad NFE AF: 0.424

Gnomad OTH AF: 0.338

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

GnomAD4 genome AF: 0.345 AC: 52392 AN: 152048 Hom.: 10731 Cov.: 33 AF XY: 0.352 AC XY: 26190 AN XY: 74326

Gnomad4 AFR AF: 0.110

Gnomad4 AMR AF: 0.447

Gnomad4 ASJ AF: 0.302

Gnomad4 EAS AF: 0.580

Gnomad4 SAS AF: 0.442

Gnomad4 FIN AF: 0.454

Gnomad4 NFE AF: 0.424

Gnomad4 OTH AF: 0.336

Alfa AF: 0.379 Hom.: 2420

Bravo AF: 0.333

Asia WGS AF: 0.477 AC: 1656 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	1.9
DANN	Benign	0.79

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: rs2239508; hg19: chr18-9845857;