chr3-128824405-A-G

Position:

• chr3-128824405-A-G

Variant summary

Our verdict is Benign. Variant got -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

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]

(HGNC:):

ACMG classification

Verdict is Benign. Variant got -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 male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High AC in GnomAd4 at 1702 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
		n.128824405A>G		intergenic_region

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RAB7A	ENST00000675864.1	c.*562A>G		3_prime_UTR_variant	6/6			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

Gnomad4 AFR AF: 0.00233

Gnomad4 AMR AF: 0.00522

Gnomad4 ASJ AF: 0.0458

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00725

Gnomad4 FIN AF: 0.0145

Gnomad4 NFE AF: 0.0168

Gnomad4 OTH AF: 0.0128

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

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs13082400; hg19: chr3-128543248;