NM_020387.4:c.-372C>A

Variant names:

• chr1-156061029-C-A
• rs2275073
• NM_020387.4:c.-372C>A

Variant summary

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

The NM_020387.4(RAB25):​c.-372C>A variant causes a upstream gene change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.615 in 173,600 control chromosomes in the GnomAD database, including 37,947 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 0.60 (32068 hom., cov: 31)
  • Exomes 𝑓: 0.71 (5879 hom.)
• Consequence: RAB25 NM_020387.4 upstream_gene
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.373
• Publications: 7 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=-0.78).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.778 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_020387.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RAB25	NM_020387.4	MANE Select	c.-372C>A		upstream_gene	N/A	NP_065120.2
	RAB25	NR_133653.2		n.-131C>A		upstream_gene	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RAB25	ENST00000361084.10	TSL:1 MANE Select	c.-372C>A		upstream_gene	N/A	ENSP00000354376.5
	RAB25	ENST00000876131.1		c.-372C>A		upstream_gene	N/A	ENSP00000546190.1
	RAB25	ENST00000921090.1		c.-372C>A		upstream_gene	N/A	ENSP00000591149.1

Frequencies

GnomAD3 genomes AF: 0.603 AC: 91531 AN: 151892 Hom.: 32070 Cov.: 31

Gnomad AFR AF: 0.262

Gnomad AMI AF: 0.898

Gnomad AMR AF: 0.705

Gnomad ASJ AF: 0.743

Gnomad EAS AF: 0.145

Gnomad SAS AF: 0.614

Gnomad FIN AF: 0.755

Gnomad MID AF: 0.769

Gnomad NFE AF: 0.784

Gnomad OTH AF: 0.654

GnomAD4 exome AF: 0.707 AC: 15262 AN: 21588 Hom.: 5879 AF XY: 0.703 AC XY: 8081 AN XY: 11488

African (AFR) AF: 0.259 AC: 145 AN: 560

American (AMR) AF: 0.735 AC: 645 AN: 878

Ashkenazi Jewish (ASJ) AF: 0.740 AC: 453 AN: 612

East Asian (EAS) AF: 0.172 AC: 243 AN: 1412

South Asian (SAS) AF: 0.633 AC: 1197 AN: 1892

European-Finnish (FIN) AF: 0.736 AC: 624 AN: 848

Middle Eastern (MID) AF: 0.833 AC: 70 AN: 84

European-Non Finnish (NFE) AF: 0.781 AC: 10989 AN: 14068

Other (OTH) AF: 0.726 AC: 896 AN: 1234

GnomAD4 genome AF: 0.602 AC: 91522 AN: 152012 Hom.: 32068 Cov.: 31 AF XY: 0.601 AC XY: 44651 AN XY: 74324

African (AFR) AF: 0.261 AC: 10824 AN: 41444

American (AMR) AF: 0.705 AC: 10773 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.743 AC: 2576 AN: 3468

East Asian (EAS) AF: 0.145 AC: 748 AN: 5170

South Asian (SAS) AF: 0.613 AC: 2954 AN: 4816

European-Finnish (FIN) AF: 0.755 AC: 7986 AN: 10576

Middle Eastern (MID) AF: 0.759 AC: 223 AN: 294

European-Non Finnish (NFE) AF: 0.784 AC: 53249 AN: 67956

Other (OTH) AF: 0.652 AC: 1370 AN: 2102

Alfa AF: 0.717 Hom.: 22345

Bravo AF: 0.584

Asia WGS AF: 0.398 AC: 1386 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.78
CADD	Benign	0.52
DANN	Benign	0.82
PhyloP100		0.37
PromoterAI		-0.047	Neutral

Splicing

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

Other links and lift over

dbSNP: rs2275073; hg19: chr1-156030820;