rs6506699

chr18-9775569-G-Achr18-9775569-G-C

Variant summary

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

The NM_006868.4(RAB31):c.119+212G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.585 in 151,450 control chromosomes in the GnomAD database, including 26,838 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 0.58 (26838 hom., cov: 29)
• Consequence: RAB31 NM_006868.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.61

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=-0.93).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.749 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
RAB31	NM_006868.4	c.119+212G>A		intron_variant		ENST00000578921.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RAB31	ENST00000578921.6	c.119+212G>A		intron_variant		1	NM_006868.4	P1
RAB31	ENST00000578734.5	c.40-16585G>A		intron_variant, NMD_transcript_variant		3
RAB31	ENST00000581109.1	c.119+212G>A		intron_variant, NMD_transcript_variant		3
RAB31	ENST00000435762.2	n.71+212G>A		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes AF: 0.585 AC: 88508 AN: 151332 Hom.: 26808 Cov.: 29

Gnomad AFR AF: 0.757

Gnomad AMI AF: 0.655

Gnomad AMR AF: 0.573

Gnomad ASJ AF: 0.537

Gnomad EAS AF: 0.495

Gnomad SAS AF: 0.525

Gnomad FIN AF: 0.504

Gnomad MID AF: 0.589

Gnomad NFE AF: 0.509

Gnomad OTH AF: 0.558

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

GnomAD4 genome AF: 0.585 AC: 88581 AN: 151450 Hom.: 26838 Cov.: 29 AF XY: 0.583 AC XY: 43143 AN XY: 73942

Gnomad4 AFR AF: 0.756

Gnomad4 AMR AF: 0.573

Gnomad4 ASJ AF: 0.537

Gnomad4 EAS AF: 0.495

Gnomad4 SAS AF: 0.524

Gnomad4 FIN AF: 0.504

Gnomad4 NFE AF: 0.509

Gnomad4 OTH AF: 0.558

Alfa AF: 0.528 Hom.: 17704

Bravo AF: 0.598

Asia WGS AF: 0.533 AC: 1857 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
Cadd	Benign	0.036
Dann	Benign	0.78

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: rs6506699; hg19: chr18-9775566;