3-128795080-A-G

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_004637.6(RAB7A):c.-8-280A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.27 in 152,004 control chromosomes in the GnomAD database, including 7,025 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.27 (7025 hom., cov: 30)
• Consequence: RAB7A NM_004637.6 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.207

Genes affected

RAB7A (HGNC:9788): (RAB7A, member RAS oncogene family) RAB family members are small, RAS-related GTP-binding proteins that are important regulators of vesicular transport. Each RAB protein targets multiple proteins that act in exocytic / endocytic pathways. This gene encodes a RAB family member that regulates vesicle traffic in the late endosomes and also from late endosomes to lysosomes. This encoded protein is also involved in the cellular vacuolation of the VacA cytotoxin of Helicobacter pylori. Mutations at highly conserved amino acid residues in this gene have caused some forms of Charcot-Marie-Tooth (CMT) type 2 neuropathies. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.97).
• BP6: Variant 3-128795080-A-G is Benign according to our data. Variant chr3-128795080-A-G is described in ClinVar as [Benign]. Clinvar id is 671681.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.473 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
RAB7A	NM_004637.6	c.-8-280A>G		intron_variant		ENST00000265062.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RAB7A	ENST00000265062.8	c.-8-280A>G		intron_variant		1	NM_004637.6	P1

Frequencies

GnomAD3 genomes AF: 0.270 AC: 41034 AN: 151884 Hom.: 7012 Cov.: 30

Gnomad AFR AF: 0.479

Gnomad AMI AF: 0.142

Gnomad AMR AF: 0.298

Gnomad ASJ AF: 0.231

Gnomad EAS AF: 0.174

Gnomad SAS AF: 0.305

Gnomad FIN AF: 0.154

Gnomad MID AF: 0.168

Gnomad NFE AF: 0.164

Gnomad OTH AF: 0.261

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.270 AC: 41089 AN: 152004 Hom.: 7025 Cov.: 30 AF XY: 0.272 AC XY: 20213 AN XY: 74324

Gnomad4 AFR AF: 0.479

Gnomad4 AMR AF: 0.298

Gnomad4 ASJ AF: 0.231

Gnomad4 EAS AF: 0.173

Gnomad4 SAS AF: 0.304

Gnomad4 FIN AF: 0.154

Gnomad4 NFE AF: 0.165

Gnomad4 OTH AF: 0.264

Alfa AF: 0.148 Hom.: 562

Bravo AF: 0.288

Asia WGS AF: 0.285 AC: 993 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jun 19, 2018

This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
Cadd	Benign	1.9
Dann	Benign	0.63

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: rs9834608; hg19: chr3-128513923; COSMIC: COSV54045102; COSMIC: COSV54045102;