rs2279395

Positions:

• chr17-82659676-G-A
• chr17-82659676-G-T

Variant summary

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

The NM_006822.3(RAB40B):​c.265-19C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.187 in 1,610,226 control chromosomes in the GnomAD database, including 30,039 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 0.17 (2363 hom., cov: 34)
  • Exomes 𝑓: 0.19 (27676 hom.)
• Consequence: RAB40B NM_006822.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.566

Genes affected

RAB40B (HGNC:18284): (RAB40B, member RAS oncogene family) The protein encoded by this gene has similarity to a yeast protein which suggests a role of the gene product in regulating secretory vesicles. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.197 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
RAB40B	NM_006822.3	c.265-19C>T		intron_variant		ENST00000571995.6
RAB40B	XM_006722271.4	c.145-19C>T		intron_variant
RAB40B	XM_011523528.3	c.214-19C>T		intron_variant
RAB40B	XM_017024042.2	c.85-19C>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RAB40B	ENST00000571995.6	c.265-19C>T		intron_variant		1	NM_006822.3	P1

Frequencies

GnomAD3 genomes AF: 0.166 AC: 25266 AN: 152102 Hom.: 2363 Cov.: 34

Gnomad AFR AF: 0.107

Gnomad AMI AF: 0.325

Gnomad AMR AF: 0.144

Gnomad ASJ AF: 0.0934

Gnomad EAS AF: 0.208

Gnomad SAS AF: 0.0825

Gnomad FIN AF: 0.246

Gnomad MID AF: 0.0823

Gnomad NFE AF: 0.200

Gnomad OTH AF: 0.135

GnomAD3 exomes AF: 0.168 AC: 42144 AN: 250964 Hom.: 4032 AF XY: 0.164 AC XY: 22213 AN XY: 135664

Gnomad AFR exome AF: 0.104

Gnomad AMR exome AF: 0.144

Gnomad ASJ exome AF: 0.0977

Gnomad EAS exome AF: 0.197

Gnomad SAS exome AF: 0.0770

Gnomad FIN exome AF: 0.249

Gnomad NFE exome AF: 0.196

Gnomad OTH exome AF: 0.156

GnomAD4 exome AF: 0.189 AC: 275269 AN: 1458006 Hom.: 27676 Cov.: 29 AF XY: 0.185 AC XY: 134146 AN XY: 725514

Gnomad4 AFR exome AF: 0.0969

Gnomad4 AMR exome AF: 0.141

Gnomad4 ASJ exome AF: 0.0981

Gnomad4 EAS exome AF: 0.229

Gnomad4 SAS exome AF: 0.0792

Gnomad4 FIN exome AF: 0.249

Gnomad4 NFE exome AF: 0.202

Gnomad4 OTH exome AF: 0.165

GnomAD4 genome AF: 0.166 AC: 25265 AN: 152220 Hom.: 2363 Cov.: 34 AF XY: 0.166 AC XY: 12374 AN XY: 74406

Gnomad4 AFR AF: 0.107

Gnomad4 AMR AF: 0.144

Gnomad4 ASJ AF: 0.0934

Gnomad4 EAS AF: 0.208

Gnomad4 SAS AF: 0.0816

Gnomad4 FIN AF: 0.246

Gnomad4 NFE AF: 0.200

Gnomad4 OTH AF: 0.134

Alfa AF: 0.167 Hom.: 3108

Bravo AF: 0.154

Asia WGS AF: 0.122 AC: 426 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	3.5
DANN	Benign	0.35

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: rs2279395; hg19: chr17-80617552; COSMIC: COSV53915398; COSMIC: COSV53915398;