NM_006868.4:c.119+212G>A

Variant names:

• chr18-9775569-G-A
• rs6506699
• NM_006868.4:c.119+212G>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.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
• Publications: 4 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=-0.93).
• 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 rank	MANE	Protein	UniProt
RAB31	NM_006868.4	c.119+212G>A		intron_variant	Intron 2 of 6	ENST00000578921.6	NP_006859.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RAB31	ENST00000578921.6	c.119+212G>A		intron_variant	Intron 2 of 6	1	NM_006868.4	ENSP00000461945.2
RAB31	ENST00000435762.2	n.71+212G>A		intron_variant	Intron 1 of 2	3
RAB31	ENST00000578734.5	n.40-16585G>A		intron_variant	Intron 1 of 5	3		ENSP00000462164.2
RAB31	ENST00000581109.1	n.119+212G>A		intron_variant	Intron 2 of 4	3		ENSP00000464046.2

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

African (AFR) AF: 0.756 AC: 31216 AN: 41278

American (AMR) AF: 0.573 AC: 8725 AN: 15234

Ashkenazi Jewish (ASJ) AF: 0.537 AC: 1862 AN: 3468

East Asian (EAS) AF: 0.495 AC: 2539 AN: 5126

South Asian (SAS) AF: 0.524 AC: 2512 AN: 4792

European-Finnish (FIN) AF: 0.504 AC: 5241 AN: 10392

Middle Eastern (MID) AF: 0.585 AC: 172 AN: 294

European-Non Finnish (NFE) AF: 0.509 AC: 34544 AN: 67852

Other (OTH) AF: 0.558 AC: 1173 AN: 2102

Alfa AF: 0.561 Hom.: 32692

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
PhyloP100		-2.6
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: rs6506699; hg19: chr18-9775566;