18-9729897-T-C

Position:

• chr18-9729897-T-C

Variant summary

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

The NM_006868.4(RAB31):​c.39+21453T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.299 in 152,164 control chromosomes in the GnomAD database, including 8,178 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 0.30 (8178 hom., cov: 32)
• Consequence: RAB31 NM_006868.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.141

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=-0.98).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.489 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RAB31	NM_006868.4	c.39+21453T>C		intron_variant		ENST00000578921.6	NP_006859.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RAB31	ENST00000578921.6	c.39+21453T>C		intron_variant		1	NM_006868.4	ENSP00000461945.2
RAB31	ENST00000578734.5	n.39+21453T>C		intron_variant		3		ENSP00000462164.2
RAB31	ENST00000581109.1	n.39+21453T>C		intron_variant		3		ENSP00000464046.2
RAB31	ENST00000583137.1	n.*262+3746T>C		intron_variant		3		ENSP00000462561.2

Frequencies

GnomAD3 genomes AF: 0.299 AC: 45453 AN: 152046 Hom.: 8159 Cov.: 32

Gnomad AFR AF: 0.495

Gnomad AMI AF: 0.403

Gnomad AMR AF: 0.338

Gnomad ASJ AF: 0.149

Gnomad EAS AF: 0.330

Gnomad SAS AF: 0.163

Gnomad FIN AF: 0.137

Gnomad MID AF: 0.209

Gnomad NFE AF: 0.210

Gnomad OTH AF: 0.299

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

GnomAD4 genome AF: 0.299 AC: 45519 AN: 152164 Hom.: 8178 Cov.: 32 AF XY: 0.293 AC XY: 21774 AN XY: 74394

Gnomad4 AFR AF: 0.495

Gnomad4 AMR AF: 0.338

Gnomad4 ASJ AF: 0.149

Gnomad4 EAS AF: 0.330

Gnomad4 SAS AF: 0.163

Gnomad4 FIN AF: 0.137

Gnomad4 NFE AF: 0.210

Gnomad4 OTH AF: 0.298

Alfa AF: 0.224 Hom.: 8364

Bravo AF: 0.327

Asia WGS AF: 0.241 AC: 837 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	2.4
DANN	Benign	0.51

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: rs7228240; hg19: chr18-9729894;