chr3-19961536-A-G

Position:

• chr3-19961536-A-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BS1 BS2

The NM_004162.5(RAB5A):​c.163+10475A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0119 in 152,354 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 0.012 (22 hom., cov: 33)
• Consequence: RAB5A NM_004162.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.10

Genes affected

RAB5A (HGNC:9783): (RAB5A, member RAS oncogene family) Enables GDP binding activity; GTP binding activity; and GTPase activity. Involved in several processes, including amyloid-beta clearance by transcytosis; early endosome to late endosome transport; and regulation of exocytosis. Located in several cellular components, including cytoplasmic side of early endosome membrane; nucleoplasm; and terminal bouton. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BS1: Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.0119 (1809/152354) while in subpopulation NFE AF= 0.0158 (1075/68040). AF 95% confidence interval is 0.015. There are 22 homozygotes in gnomad4. There are 834 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.
• BS2: High AC in GnomAd4 at 1809 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
RAB5A	NM_004162.5	c.163+10475A>G		intron_variant		ENST00000273047.9
RAB5A	NM_001292048.2	c.163+10475A>G		intron_variant
RAB5A	XM_047448648.1	c.-268-9012A>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RAB5A	ENST00000273047.9	c.163+10475A>G		intron_variant		1	NM_004162.5	P1

Frequencies

GnomAD3 genomes AF: 0.0119 AC: 1811 AN: 152236 Hom.: 23 Cov.: 33

Gnomad AFR AF: 0.00292

Gnomad AMI AF: 0.0526

Gnomad AMR AF: 0.0126

Gnomad ASJ AF: 0.0734

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.0134

Gnomad FIN AF: 0.00132

Gnomad MID AF: 0.0253

Gnomad NFE AF: 0.0158

Gnomad OTH AF: 0.0158

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

GnomAD4 genome AF: 0.0119 AC: 1809 AN: 152354 Hom.: 22 Cov.: 33 AF XY: 0.0112 AC XY: 834 AN XY: 74516

Gnomad4 AFR AF: 0.00291

Gnomad4 AMR AF: 0.0125

Gnomad4 ASJ AF: 0.0734

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.0130

Gnomad4 FIN AF: 0.00132

Gnomad4 NFE AF: 0.0158

Gnomad4 OTH AF: 0.0156

Alfa AF: 0.0115 Hom.: 2

Bravo AF: 0.0121

Asia WGS AF: 0.00607 AC: 21 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	12
DANN	Benign	0.70

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: rs7627396; hg19: chr3-20003028;