18-74352475-T-G

Variant summary

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

The NM_001174123.2(C18orf63):c.979-771T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.498 in 151,688 control chromosomes in the GnomAD database, including 19,609 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 0.50 (19609 hom., cov: 32)
• Consequence: C18orf63 NM_001174123.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0840

Genes affected

C18orf63 (HGNC:40037): (chromosome 18 open reading frame 63)

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.575 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
C18orf63	NM_001174123.2	c.979-771T>G		intron_variant		ENST00000579455.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
C18orf63	ENST00000579455.2	c.979-771T>G		intron_variant		1	NM_001174123.2	P1

Frequencies

GnomAD3 genomes AF: 0.498 AC: 75455 AN: 151572 Hom.: 19611 Cov.: 32

Gnomad AFR AF: 0.354

Gnomad AMI AF: 0.734

Gnomad AMR AF: 0.448

Gnomad ASJ AF: 0.670

Gnomad EAS AF: 0.453

Gnomad SAS AF: 0.437

Gnomad FIN AF: 0.571

Gnomad MID AF: 0.570

Gnomad NFE AF: 0.579

Gnomad OTH AF: 0.525

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

GnomAD4 genome AF: 0.498 AC: 75472 AN: 151688 Hom.: 19609 Cov.: 32 AF XY: 0.495 AC XY: 36700 AN XY: 74130

Gnomad4 AFR AF: 0.354

Gnomad4 AMR AF: 0.447

Gnomad4 ASJ AF: 0.670

Gnomad4 EAS AF: 0.452

Gnomad4 SAS AF: 0.436

Gnomad4 FIN AF: 0.571

Gnomad4 NFE AF: 0.579

Gnomad4 OTH AF: 0.526

Alfa AF: 0.442 Hom.: 2089

Bravo AF: 0.482

Asia WGS AF: 0.448 AC: 1556 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
Cadd	Benign	2.9
Dann	Benign	0.40

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: rs1476112; hg19: chr18-72019710;