18-9743053-T-G

Position:

• chr18-9743053-T-G

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The ENST00000578921.6(RAB31):​c.40-32225T>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 152,140 control chromosomes in the GnomAD database, including 7,226 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.28 (7226 hom., cov: 33)
• Consequence: RAB31 ENST00000578921.6 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.06

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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BP6: Variant 18-9743053-T-G is Benign according to our data. Variant chr18-9743053-T-G is described in ClinVar as [Benign]. Clinvar id is 1255287.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.641 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RAB31	NM_006868.4	c.40-32225T>G		intron_variant		ENST00000578921.6	NP_006859.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RAB31	ENST00000578921.6	c.40-32225T>G		intron_variant		1	NM_006868.4	ENSP00000461945.2
RAB31	ENST00000578734.5	n.39+34609T>G		intron_variant		3		ENSP00000462164.2
RAB31	ENST00000581109.1	n.40-32225T>G		intron_variant		3		ENSP00000464046.2
RAB31	ENST00000583137.1	n.*263-14910T>G		intron_variant		3		ENSP00000462561.2

Frequencies

GnomAD3 genomes AF: 0.279 AC: 42357 AN: 152022 Hom.: 7218 Cov.: 33

Gnomad AFR AF: 0.393

Gnomad AMI AF: 0.221

Gnomad AMR AF: 0.402

Gnomad ASJ AF: 0.174

Gnomad EAS AF: 0.660

Gnomad SAS AF: 0.209

Gnomad FIN AF: 0.171

Gnomad MID AF: 0.187

Gnomad NFE AF: 0.181

Gnomad OTH AF: 0.269

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

GnomAD4 genome AF: 0.279 AC: 42407 AN: 152140 Hom.: 7226 Cov.: 33 AF XY: 0.281 AC XY: 20879 AN XY: 74374

Gnomad4 AFR AF: 0.393

Gnomad4 AMR AF: 0.403

Gnomad4 ASJ AF: 0.174

Gnomad4 EAS AF: 0.660

Gnomad4 SAS AF: 0.209

Gnomad4 FIN AF: 0.171

Gnomad4 NFE AF: 0.181

Gnomad4 OTH AF: 0.270

Alfa AF: 0.213 Hom.: 3872

Bravo AF: 0.309

Asia WGS AF: 0.374 AC: 1297 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jan 18, 2019

This variant is associated with the following publications: (PMID: 30182384) -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	1.1
DANN	Benign	0.20

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: rs6506689; hg19: chr18-9743050;