NM_006868.4:c.40-25396G>A

Variant names:

• chr18-9749882-G-A
• rs9951171
• NM_006868.4:c.40-25396G>A

Variant summary

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

The NM_006868.4(RAB31):​c.40-25396G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.443 in 151,988 control chromosomes in the GnomAD database, including 14,977 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 0.44 (14977 hom., cov: 32)
• Consequence: RAB31 NM_006868.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.243
• Publications: 19 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=-0.86).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.491 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RAB31	NM_006868.4	c.40-25396G>A		intron_variant	Intron 1 of 6	ENST00000578921.6	NP_006859.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RAB31	ENST00000578921.6	c.40-25396G>A		intron_variant	Intron 1 of 6	1	NM_006868.4	ENSP00000461945.2
RAB31	ENST00000578734.5	n.39+41438G>A		intron_variant	Intron 1 of 5	3		ENSP00000462164.2
RAB31	ENST00000581109.1	n.40-25396G>A		intron_variant	Intron 1 of 4	3		ENSP00000464046.2
RAB31	ENST00000583137.1	n.*263-8081G>A		intron_variant	Intron 4 of 4	3		ENSP00000462561.2

Frequencies

GnomAD3 genomes AF: 0.443 AC: 67350 AN: 151870 Hom.: 14960 Cov.: 32

Gnomad AFR AF: 0.448

Gnomad AMI AF: 0.442

Gnomad AMR AF: 0.450

Gnomad ASJ AF: 0.548

Gnomad EAS AF: 0.454

Gnomad SAS AF: 0.508

Gnomad FIN AF: 0.380

Gnomad MID AF: 0.408

Gnomad NFE AF: 0.438

Gnomad OTH AF: 0.447

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

GnomAD4 genome AF: 0.443 AC: 67402 AN: 151988 Hom.: 14977 Cov.: 32 AF XY: 0.442 AC XY: 32812 AN XY: 74270

African (AFR) AF: 0.448 AC: 18569 AN: 41424

American (AMR) AF: 0.450 AC: 6881 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.548 AC: 1901 AN: 3468

East Asian (EAS) AF: 0.453 AC: 2337 AN: 5156

South Asian (SAS) AF: 0.507 AC: 2442 AN: 4814

European-Finnish (FIN) AF: 0.380 AC: 4017 AN: 10568

Middle Eastern (MID) AF: 0.412 AC: 121 AN: 294

European-Non Finnish (NFE) AF: 0.438 AC: 29784 AN: 67968

Other (OTH) AF: 0.450 AC: 949 AN: 2110

Alfa AF: 0.439 Hom.: 40249

Bravo AF: 0.444

Asia WGS AF: 0.520 AC: 1810 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	4.3
DANN	Benign	0.64
PhyloP100		0.24
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: rs9951171; hg19: chr18-9749879;