1-156070519-A-G

Variant names:

• chr1-156070519-A-G
• rs2275075
• NM_020387.4:c.*232A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_020387.4(RAB25):​c.*232A>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
• Publications: 13 publications found

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

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
RAB25	NM_020387.4	c.*232A>G		downstream_gene_variant		ENST00000361084.10	NP_065120.2
RAB25	NR_133653.2	n.*15A>G		downstream_gene_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RAB25	ENST00000361084.10	c.*232A>G		downstream_gene_variant		1	NM_020387.4	ENSP00000354376.5
RAB25	ENST00000497968.1	n.*154A>G		downstream_gene_variant		1
RAB25	ENST00000473336.5	n.*15A>G		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

African (AFR) AF: 0.469 AC: 4928 AN: 10510

American (AMR) AF: 0.771 AC: 10314 AN: 13382

Ashkenazi Jewish (ASJ) AF: 0.805 AC: 8893 AN: 11044

East Asian (EAS) AF: 0.138 AC: 3358 AN: 24340

South Asian (SAS) AF: 0.694 AC: 26273 AN: 37834

European-Finnish (FIN) AF: 0.784 AC: 17175 AN: 21902

Middle Eastern (MID) AF: 0.807 AC: 1284 AN: 1592

European-Non Finnish (NFE) AF: 0.808 AC: 189692 AN: 234902

Other (OTH) AF: 0.736 AC: 15768 AN: 21426

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

African (AFR) AF: 0.474 AC: 19587 AN: 41314

American (AMR) AF: 0.746 AC: 11395 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.815 AC: 2826 AN: 3468

East Asian (EAS) AF: 0.146 AC: 754 AN: 5168

South Asian (SAS) AF: 0.666 AC: 3210 AN: 4818

European-Finnish (FIN) AF: 0.779 AC: 8248 AN: 10582

Middle Eastern (MID) AF: 0.791 AC: 231 AN: 292

European-Non Finnish (NFE) AF: 0.810 AC: 55046 AN: 67940

Other (OTH) AF: 0.716 AC: 1507 AN: 2106

Alfa AF: 0.766 Hom.: 131051

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
PhyloP100		-0.026
Mutation Taster		=95/5	polymorphism

Splicing

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

Other links and lift over

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