1-229299529-A-G

Variant names:

• chr1-229299529-A-G
• rs237779
• NM_004578.4:c.541+457A>G

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 5 publications found

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

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_004578.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RAB4A	NM_004578.4	MANE Select	c.541+457A>G		intron	N/A	NP_004569.2
	RAB4A	NM_001271998.2		c.226+457A>G		intron	N/A	NP_001258927.1
	RAB4A	NR_073545.2		n.732+457A>G		intron	N/A

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RAB4A	ENST00000366690.5	TSL:1 MANE Select	c.541+457A>G		intron	N/A	ENSP00000355651.4
	RAB4A	ENST00000618010.4	TSL:3	c.226+457A>G		intron	N/A	ENSP00000482077.1
	RAB4A	ENST00000473894.1	TSL:3	n.491+457A>G		intron	N/A

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

African (AFR) AF: 0.320 AC: 13249 AN: 41444

American (AMR) AF: 0.145 AC: 2217 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.219 AC: 761 AN: 3470

East Asian (EAS) AF: 0.0983 AC: 510 AN: 5186

South Asian (SAS) AF: 0.142 AC: 685 AN: 4812

European-Finnish (FIN) AF: 0.190 AC: 2007 AN: 10566

Middle Eastern (MID) AF: 0.119 AC: 35 AN: 294

European-Non Finnish (NFE) AF: 0.207 AC: 14097 AN: 67972

Other (OTH) AF: 0.185 AC: 389 AN: 2106

Alfa AF: 0.209 Hom.: 2170

Bravo AF: 0.224

Asia WGS AF: 0.123 AC: 430 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	5.2
DANN	Benign	0.58
PhyloP100		0.072
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs237779; hg19: chr1-229435276;