18-9857288-T-C

Variant names:

• chr18-9857288-T-C
• rs2017791
• NM_006868.4:c.491-1940T>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_006868.4(RAB31):​c.491-1940T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.366 in 151,996 control chromosomes in the GnomAD database, including 10,807 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 0.37 (10807 hom., cov: 31)
• Consequence: RAB31 NM_006868.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0770
• Publications: 6 publications found

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

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.564 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RAB31	NM_006868.4	c.491-1940T>C		intron_variant	Intron 6 of 6	ENST00000578921.6	NP_006859.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RAB31	ENST00000578921.6	c.491-1940T>C		intron_variant	Intron 6 of 6	1	NM_006868.4	ENSP00000461945.2

Frequencies

GnomAD3 genomes AF: 0.366 AC: 55569 AN: 151880 Hom.: 10809 Cov.: 31

Gnomad AFR AF: 0.244

Gnomad AMI AF: 0.463

Gnomad AMR AF: 0.455

Gnomad ASJ AF: 0.281

Gnomad EAS AF: 0.583

Gnomad SAS AF: 0.455

Gnomad FIN AF: 0.429

Gnomad MID AF: 0.259

Gnomad NFE AF: 0.392

Gnomad OTH AF: 0.337

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

GnomAD4 genome AF: 0.366 AC: 55584 AN: 151996 Hom.: 10807 Cov.: 31 AF XY: 0.374 AC XY: 27776 AN XY: 74306

African (AFR) AF: 0.244 AC: 10134 AN: 41460

American (AMR) AF: 0.455 AC: 6945 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.281 AC: 975 AN: 3470

East Asian (EAS) AF: 0.582 AC: 2994 AN: 5148

South Asian (SAS) AF: 0.455 AC: 2189 AN: 4816

European-Finnish (FIN) AF: 0.429 AC: 4533 AN: 10556

Middle Eastern (MID) AF: 0.248 AC: 73 AN: 294

European-Non Finnish (NFE) AF: 0.392 AC: 26614 AN: 67954

Other (OTH) AF: 0.334 AC: 706 AN: 2112

Alfa AF: 0.371 Hom.: 17810

Bravo AF: 0.362

Asia WGS AF: 0.497 AC: 1727 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	7.7
DANN	Benign	0.66
PhyloP100		0.077
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs2017791; hg19: chr18-9857285;