3-128795495-G-A

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BS1 BS2

The NM_004637.6(RAB7A):c.53+75G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0031 in 1,365,360 control chromosomes in the GnomAD database, including 78 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.012 (31 hom., cov: 31)
  • Exomes 𝑓: 0.0020 (47 hom.)
• Consequence: RAB7A NM_004637.6 intron
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.19

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=-0.9).
• BP6: Variant 3-128795495-G-A is Benign according to our data. Variant chr3-128795495-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 1211274.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.0119 (1818/152206) while in subpopulation AFR AF= 0.0391 (1624/41528). AF 95% confidence interval is 0.0375. There are 31 homozygotes in gnomad4. There are 859 alleles in male gnomad4 subpopulation. Median coverage is 31. This position pass quality control queck.
• BS2: High AC in GnomAd at 1813 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
RAB7A	NM_004637.6	c.53+75G>A		intron_variant		ENST00000265062.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RAB7A	ENST00000265062.8	c.53+75G>A		intron_variant		1	NM_004637.6	P1

Frequencies

GnomAD3 genomes AF: 0.0119 AC: 1813 AN: 152088 Hom.: 32 Cov.: 31

Gnomad AFR AF: 0.0390

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00727

Gnomad ASJ AF: 0.00606

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.0222

Gnomad NFE AF: 0.000515

Gnomad OTH AF: 0.0110

GnomAD4 exome AF: 0.00199 AC: 2418 AN: 1213154 Hom.: 47 AF XY: 0.00184 AC XY: 1135 AN XY: 615642

Gnomad4 AFR exome AF: 0.0436

Gnomad4 AMR exome AF: 0.00503

Gnomad4 ASJ exome AF: 0.00755

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000148

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.000497

Gnomad4 OTH exome AF: 0.00538

GnomAD4 genome AF: 0.0119 AC: 1818 AN: 152206 Hom.: 31 Cov.: 31 AF XY: 0.0115 AC XY: 859 AN XY: 74416

Gnomad4 AFR AF: 0.0391

Gnomad4 AMR AF: 0.00726

Gnomad4 ASJ AF: 0.00606

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000515

Gnomad4 OTH AF: 0.0109

Alfa AF: 0.00717 Hom.: 6

Bravo AF: 0.0147

Asia WGS AF: 0.00462 AC: 16 AN: 3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

GeneDx

Aug 03, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
Cadd	Benign	0.040
Dann	Benign	0.43

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: rs149563047; hg19: chr3-128514338;