rs7203694

Variant names:

• chr16-602941-G-A
• rs7203694
• NM_021168.5:c.142+12508G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_021168.5(RAB40C):​c.142+12508G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.176 in 152,160 control chromosomes in the GnomAD database, including 2,562 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 0.18 (2562 hom., cov: 32)
• Consequence: RAB40C NM_021168.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.29
• Publications: 13 publications found

Genes affected

RAB40C (HGNC:18285): (RAB40C, member RAS oncogene family) Predicted to enable GDP binding activity; GTP binding activity; and GTPase activity. Predicted to be involved in protein localization to plasma membrane. Predicted to be located in perinuclear region of cytoplasm. Predicted to be active in endosome; plasma membrane; and synaptic vesicle. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.03).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.244 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RAB40C	NM_021168.5	c.142+12508G>A		intron_variant	Intron 1 of 5	ENST00000248139.8	NP_066991.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RAB40C	ENST00000248139.8	c.142+12508G>A		intron_variant	Intron 1 of 5	1	NM_021168.5	ENSP00000248139.3

Frequencies

GnomAD3 genomes AF: 0.175 AC: 26675 AN: 152042 Hom.: 2556 Cov.: 32

Gnomad AFR AF: 0.179

Gnomad AMI AF: 0.204

Gnomad AMR AF: 0.112

Gnomad ASJ AF: 0.156

Gnomad EAS AF: 0.0279

Gnomad SAS AF: 0.256

Gnomad FIN AF: 0.196

Gnomad MID AF: 0.117

Gnomad NFE AF: 0.192

Gnomad OTH AF: 0.138

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

GnomAD4 genome AF: 0.176 AC: 26707 AN: 152160 Hom.: 2562 Cov.: 32 AF XY: 0.175 AC XY: 13039 AN XY: 74386

African (AFR) AF: 0.180 AC: 7454 AN: 41502

American (AMR) AF: 0.112 AC: 1709 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.156 AC: 541 AN: 3470

East Asian (EAS) AF: 0.0280 AC: 145 AN: 5182

South Asian (SAS) AF: 0.256 AC: 1235 AN: 4824

European-Finnish (FIN) AF: 0.196 AC: 2074 AN: 10598

Middle Eastern (MID) AF: 0.122 AC: 36 AN: 294

European-Non Finnish (NFE) AF: 0.192 AC: 13032 AN: 67980

Other (OTH) AF: 0.140 AC: 295 AN: 2114

Alfa AF: 0.188 Hom.: 1638

Bravo AF: 0.166

Asia WGS AF: 0.170 AC: 592 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.90
DANN	Benign	0.16
PhyloP100		-1.3
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: rs7203694; hg19: chr16-652941;