1-156070519-A-G

Variant summary

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

The 1-156070519-A-G variant causes a downstream gene change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.721 in 528,804 control chromosomes in the GnomAD database, including 145,833 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 0.68 (37764 hom., cov: 30)
  • Exomes 𝑓: 0.74 (108069 hom.)
• Consequence: RAB25 NM_020387.4 downstream_gene
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0260

Genes affected

RAB25 (HGNC:18238): (RAB25, member RAS oncogene family) The protein encoded by this gene is a member of the RAS superfamily of small GTPases. The encoded protein is involved in membrane trafficking and cell survival. This gene has been found to be a tumor suppressor and an oncogene, depending on the context. Two variants, one protein-coding and the other not, have been found for this gene. [provided by RefSeq, Nov 2015]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.805 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
RAB25	NM_020387.4			downstream_gene_variant		ENST00000361084.10
RAB25	NR_133653.2			downstream_gene_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RAB25	ENST00000361084.10			downstream_gene_variant		1	NM_020387.4	P1
RAB25	ENST00000473336.5			downstream_gene_variant		2

Frequencies

GnomAD3 genomes AF: 0.682 AC: 103572 AN: 151756 Hom.: 37735 Cov.: 30

Gnomad AFR AF: 0.473

Gnomad AMI AF: 0.923

Gnomad AMR AF: 0.746

Gnomad ASJ AF: 0.815

Gnomad EAS AF: 0.146

Gnomad SAS AF: 0.667

Gnomad FIN AF: 0.779

Gnomad MID AF: 0.794

Gnomad NFE AF: 0.810

Gnomad OTH AF: 0.718

GnomAD4 exome AF: 0.737 AC: 277685 AN: 376932 Hom.: 108069 Cov.: 5 AF XY: 0.738 AC XY: 145294 AN XY: 196934

Gnomad4 AFR exome AF: 0.469

Gnomad4 AMR exome AF: 0.771

Gnomad4 ASJ exome AF: 0.805

Gnomad4 EAS exome AF: 0.138

Gnomad4 SAS exome AF: 0.694

Gnomad4 FIN exome AF: 0.784

Gnomad4 NFE exome AF: 0.808

Gnomad4 OTH exome AF: 0.736

GnomAD4 genome AF: 0.682 AC: 103646 AN: 151872 Hom.: 37764 Cov.: 30 AF XY: 0.680 AC XY: 50446 AN XY: 74238

Gnomad4 AFR AF: 0.474

Gnomad4 AMR AF: 0.746

Gnomad4 ASJ AF: 0.815

Gnomad4 EAS AF: 0.146

Gnomad4 SAS AF: 0.666

Gnomad4 FIN AF: 0.779

Gnomad4 NFE AF: 0.810

Gnomad4 OTH AF: 0.716

Alfa AF: 0.791 Hom.: 62052

Bravo AF: 0.668

Asia WGS AF: 0.445 AC: 1550 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
Cadd	Benign	8.0
Dann	Benign	0.74

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs2275075; hg19: chr1-156040310; COSMIC: COSV63108918;