3-128824405-A-G

Variant names:

• chr3-128824405-A-G
• rs13082400
• ENST00000675864.1:c.*562A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BS1 BS2

The ENST00000675864.1(RAB7A):​c.*562A>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0112 in 152,368 control chromosomes in the GnomAD database, including 22 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 0.011 (22 hom., cov: 32)
• Consequence: RAB7A ENST00000675864.1 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0190
• Publications: 1 publications found

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]

RAB7A Gene-Disease associations (from GenCC):

• Charcot-Marie-Tooth disease type 2

  Inheritance: AD Classification: DEFINITIVE Submitted by: ClinGen
• Charcot-Marie-Tooth disease type 2B

  Inheritance: AD Classification: STRONG, SUPPORTIVE Submitted by: Orphanet, Labcorp Genetics (formerly Invitae)

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).
• BS1: Variant frequency is greater than expected in population nfe. GnomAd4 allele frequency = 0.0112 (1702/152368) while in subpopulation NFE AF = 0.0168 (1144/68034). AF 95% confidence interval is 0.016. There are 22 homozygotes in GnomAd4. There are 818 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.
• BS2: High AC in GnomAd4 at 1702 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RAB7A	ENST00000675864.1	c.*562A>G		3_prime_UTR_variant	Exon 6 of 6			ENSP00000502566.1

Frequencies

GnomAD3 genomes AF: 0.0112 AC: 1703 AN: 152250 Hom.: 22 Cov.: 32

Gnomad AFR AF: 0.00234

Gnomad AMI AF: 0.00110

Gnomad AMR AF: 0.00523

Gnomad ASJ AF: 0.0458

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00724

Gnomad FIN AF: 0.0145

Gnomad MID AF: 0.0190

Gnomad NFE AF: 0.0168

Gnomad OTH AF: 0.0129

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

GnomAD4 genome AF: 0.0112 AC: 1702 AN: 152368 Hom.: 22 Cov.: 32 AF XY: 0.0110 AC XY: 818 AN XY: 74510

African (AFR) AF: 0.00233 AC: 97 AN: 41588

American (AMR) AF: 0.00522 AC: 80 AN: 15312

Ashkenazi Jewish (ASJ) AF: 0.0458 AC: 159 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5188

South Asian (SAS) AF: 0.00725 AC: 35 AN: 4828

European-Finnish (FIN) AF: 0.0145 AC: 154 AN: 10624

Middle Eastern (MID) AF: 0.0170 AC: 5 AN: 294

European-Non Finnish (NFE) AF: 0.0168 AC: 1144 AN: 68034

Other (OTH) AF: 0.0128 AC: 27 AN: 2116

Alfa AF: 0.0174 Hom.: 0

Bravo AF: 0.0104

Asia WGS AF: 0.000577 AC: 2 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	3.4
DANN	Benign	0.77
PhyloP100		-0.019

Splicing

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

Other links and lift over

dbSNP: rs13082400; hg19: chr3-128543248;