chr18-54362334-T-C

Variant names:

• chr18-54362334-T-C
• rs142068230
• NM_001288980.2:c.975T>C

Variant summary

Our verdict is Benign. The variant received -9 ACMG points: 0P and 9B. BP4_Moderate BP6_Moderate BP7 BS2

The NM_001288980.2(C18orf54):​c.975T>C​(p.Asp325Asp) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00289 in 1,535,992 control chromosomes in the GnomAD database, including 14 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0017 (1 hom., cov: 33)
  • Exomes 𝑓: 0.0030 (13 hom.)
• Consequence: C18orf54 NM_001288980.2 synonymous
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.109
• Publications: 0 publications found

Genes affected

C18orf54 (HGNC:13796): (chromosome 18 open reading frame 54) Predicted to act upstream of or within negative regulation of cell population proliferation. Predicted to be located in extracellular region. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Benign. The variant received -9 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.34).
• BP6: Variant 18-54362334-T-C is Benign according to our data. Variant chr18-54362334-T-C is described in ClinVar as Likely_benign. ClinVar VariationId is 2648732.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=-0.109 with no splicing effect.
• BS2: High Homozygotes in GnomAdExome4 at 13 AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001288980.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	C18orf54	NM_001288980.2	MANE Select	c.975T>C	p.Asp325Asp	synonymous	Exon 4 of 9	NP_001275909.1
	C18orf54	NM_001288981.2		c.975T>C	p.Asp325Asp	synonymous	Exon 4 of 9	NP_001275910.1
	C18orf54	NM_001370309.1		c.975T>C	p.Asp325Asp	synonymous	Exon 3 of 8	NP_001357238.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	C18orf54	ENST00000620105.5	TSL:1 MANE Select	c.975T>C	p.Asp325Asp	synonymous	Exon 4 of 9	ENSP00000477654.1	Q8IYD9-2
	C18orf54	ENST00000300091.5	TSL:1	c.589+386T>C		intron	N/A	ENSP00000300091.5	Q8IYD9-1
	C18orf54	ENST00000893216.1		c.975T>C	p.Asp325Asp	synonymous	Exon 3 of 9	ENSP00000563275.1

Frequencies

GnomAD3 genomes AF: 0.00175 AC: 266 AN: 152248 Hom.: 1 Cov.: 33

Gnomad AFR AF: 0.000627

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000327

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.000753

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00332

Gnomad OTH AF: 0.000478

GnomAD2 exomes AF: 0.00164 AC: 225 AN: 137362 AF XY: 0.00158

Gnomad AFR exome AF: 0.000460

Gnomad AMR exome AF: 0.000327

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00129

Gnomad NFE exome AF: 0.00369

Gnomad OTH exome AF: 0.00143

GnomAD4 exome AF: 0.00301 AC: 4168 AN: 1383626 Hom.: 13 Cov.: 32 AF XY: 0.00303 AC XY: 2071 AN XY: 682762

African (AFR) AF: 0.000285 AC: 9 AN: 31588

American (AMR) AF: 0.000364 AC: 13 AN: 35696

Ashkenazi Jewish (ASJ) AF: 0.0000397 AC: 1 AN: 25176

East Asian (EAS) AF: 0.00 AC: 0 AN: 35714

South Asian (SAS) AF: 0.0000126 AC: 1 AN: 79208

European-Finnish (FIN) AF: 0.00144 AC: 49 AN: 33922

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5694

European-Non Finnish (NFE) AF: 0.00370 AC: 3988 AN: 1078706

Other (OTH) AF: 0.00185 AC: 107 AN: 57922

GnomAD4 genome AF: 0.00175 AC: 266 AN: 152366 Hom.: 1 Cov.: 33 AF XY: 0.00126 AC XY: 94 AN XY: 74508

African (AFR) AF: 0.000625 AC: 26 AN: 41590

American (AMR) AF: 0.000327 AC: 5 AN: 15306

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5192

South Asian (SAS) AF: 0.00 AC: 0 AN: 4828

European-Finnish (FIN) AF: 0.000753 AC: 8 AN: 10620

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.00332 AC: 226 AN: 68040

Other (OTH) AF: 0.000473 AC: 1 AN: 2116

Alfa AF: 0.00179 Hom.: 0

Bravo AF: 0.00163

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.34
CADD	Benign	6.1
DANN	Benign	0.72
PhyloP100		-0.11
Mutation Taster		=100/0	polymorphism

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: rs142068230; hg19: chr18-51888704;