rs74127323

Variant names:

• chr10-27504350-C-G
• rs74127323
• NM_021252.5:c.-20C>G

Your query was ambiguous. Multiple possible variants found:

• chr10-27504350-C-G
• chr10-27504350-C-T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_021252.5(RAB18):​c.-20C>G variant causes a 5 prime UTR premature start codon gain change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000141 in 1,416,368 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: not found (cov: 32)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: RAB18 NM_021252.5 5_prime_UTR_premature_start_codon_gain
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.592
• Publications: 0 publications found

Genes affected

RAB18 (HGNC:14244): (RAB18, member RAS oncogene family) The protein encoded by this gene is a member of a family of Ras-related small GTPases that regulate membrane trafficking in organelles and transport vesicles. Knockdown studies is zebrafish suggest that this protein may have a role in eye and brain development. Mutations in this gene are associated with Warburg micro syndrome type 3. Alternatively spliced transcript variants have been found for this gene. [provided by RefSeq, Jan 2012]

RAB18 Gene-Disease associations (from GenCC):

• Warburg micro syndrome 3

  Inheritance: AR Classification: DEFINITIVE, STRONG Submitted by: G2P, Labcorp Genetics (formerly Invitae)
• Warburg micro syndrome

  Inheritance: AR Classification: MODERATE, SUPPORTIVE Submitted by: ClinGen, Orphanet

LOC124902399 (HGNC:):

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.65).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RAB18	NM_021252.5	c.-20C>G		5_prime_UTR_premature_start_codon_gain_variant	Exon 1 of 7	ENST00000356940.11	NP_067075.1
RAB18	NM_021252.5	c.-20C>G		5_prime_UTR_variant	Exon 1 of 7	ENST00000356940.11	NP_067075.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RAB18	ENST00000356940.11	c.-20C>G		5_prime_UTR_premature_start_codon_gain_variant	Exon 1 of 7	1	NM_021252.5	ENSP00000349415.7
RAB18	ENST00000356940.11	c.-20C>G		5_prime_UTR_variant	Exon 1 of 7	1	NM_021252.5	ENSP00000349415.7

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000141 AC: 2 AN: 1416368 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 699996

African (AFR) AF: 0.00 AC: 0 AN: 32894

American (AMR) AF: 0.00 AC: 0 AN: 36972

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25284

East Asian (EAS) AF: 0.00 AC: 0 AN: 38054

South Asian (SAS) AF: 0.00 AC: 0 AN: 80496

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 49830

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4540

European-Non Finnish (NFE) AF: 0.00000184 AC: 2 AN: 1089556

Other (OTH) AF: 0.00 AC: 0 AN: 58742

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.65
CADD	Benign	12
DANN	Benign	0.77
PhyloP100		-0.59
PromoterAI		-0.099	Neutral

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: rs74127323; hg19: chr10-27793279;