1-229299529-A-G

Position:

• chr1-229299529-A-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_004578.4(RAB4A):​c.541+457A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.224 in 152,046 control chromosomes in the GnomAD database, including 4,113 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 0.22 (4113 hom., cov: 32)
• Consequence: RAB4A NM_004578.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0720

Genes affected

RAB4A (HGNC:9781): (RAB4A, member RAS oncogene family) This gene is a member of the largest group in the Ras superfamily of small GTPases, which regulate membrane trafficking. The encoded protein is associated with early endosomes and is involved in their sorting and recycling. The protein also plays a role in regulating the recycling of receptors from endosomes to the plasma membrane. Alternatively spliced transcript variants have been observed for this gene. [provided by RefSeq, Dec 2012]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.315 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
RAB4A	NM_004578.4	c.541+457A>G		intron_variant		ENST00000366690.5
RAB4A	NM_001271998.2	c.226+457A>G		intron_variant
RAB4A	NR_073545.2	n.732+457A>G		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RAB4A	ENST00000366690.5	c.541+457A>G		intron_variant		1	NM_004578.4	P1
RAB4A	ENST00000618010.4	c.226+457A>G		intron_variant		3
RAB4A	ENST00000473894.1	n.491+457A>G		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes AF: 0.224 AC: 34073 AN: 151930 Hom.: 4103 Cov.: 32

Gnomad AFR AF: 0.319

Gnomad AMI AF: 0.185

Gnomad AMR AF: 0.145

Gnomad ASJ AF: 0.219

Gnomad EAS AF: 0.0979

Gnomad SAS AF: 0.143

Gnomad FIN AF: 0.190

Gnomad MID AF: 0.123

Gnomad NFE AF: 0.207

Gnomad OTH AF: 0.187

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

GnomAD4 genome AF: 0.224 AC: 34118 AN: 152046 Hom.: 4113 Cov.: 32 AF XY: 0.219 AC XY: 16261 AN XY: 74338

Gnomad4 AFR AF: 0.320

Gnomad4 AMR AF: 0.145

Gnomad4 ASJ AF: 0.219

Gnomad4 EAS AF: 0.0983

Gnomad4 SAS AF: 0.142

Gnomad4 FIN AF: 0.190

Gnomad4 NFE AF: 0.207

Gnomad4 OTH AF: 0.185

Alfa AF: 0.210 Hom.: 1623

Bravo AF: 0.224

Asia WGS AF: 0.123 AC: 430 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	5.2
DANN	Benign	0.58

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: rs237779; hg19: chr1-229435276;