18-57436076-G-A

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_004852.3(ONECUT2):c.360G>A(p.Arg120=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00344 in 1,597,586 control chromosomes in the GnomAD database, including 173 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.018 (93 hom., cov: 32)
  • Exomes 𝑓: 0.0019 (80 hom.)
• Consequence: ONECUT2 NM_004852.3 synonymous
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.17

Genes affected

ONECUT2 (HGNC:8139): (one cut homeobox 2) This gene encodes a member of the onecut family of transcription factors, which are characterized by a cut domain and an atypical homeodomain. The protein binds to specific DNA sequences and stimulates expression of target genes, including genes involved in melanocyte and hepatocyte differentiation. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.68).
• BP6: Variant 18-57436076-G-A is Benign according to our data. Variant chr18-57436076-G-A is described in ClinVar as [Benign]. Clinvar id is 710665.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0613 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ONECUT2	NM_004852.3	c.360G>A	p.Arg120=	synonymous_variant	1/2	ENST00000491143.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ONECUT2	ENST00000491143.3	c.360G>A	p.Arg120=	synonymous_variant	1/2	1	NM_004852.3	P1

Frequencies

GnomAD3 genomes AF: 0.0182 AC: 2762 AN: 151956 Hom.: 93 Cov.: 32

Gnomad AFR AF: 0.0634

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00694

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00321

Gnomad NFE AF: 0.000177

Gnomad OTH AF: 0.00814

GnomAD3 exomes AF: 0.00487 AC: 1115 AN: 229018 Hom.: 34 AF XY: 0.00373 AC XY: 469 AN XY: 125766

Gnomad AFR exome AF: 0.0670

Gnomad AMR exome AF: 0.00269

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.0000660

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000219

Gnomad OTH exome AF: 0.00138

GnomAD4 exome AF: 0.00189 AC: 2734 AN: 1445518 Hom.: 80 Cov.: 34 AF XY: 0.00158 AC XY: 1134 AN XY: 719206

Gnomad4 AFR exome AF: 0.0647

Gnomad4 AMR exome AF: 0.00318

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000348

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.000160

Gnomad4 OTH exome AF: 0.00399

GnomAD4 genome AF: 0.0182 AC: 2766 AN: 152068 Hom.: 93 Cov.: 32 AF XY: 0.0169 AC XY: 1258 AN XY: 74324

Gnomad4 AFR AF: 0.0633

Gnomad4 AMR AF: 0.00687

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000177

Gnomad4 OTH AF: 0.00806

Alfa AF: 0.00708 Hom.: 6

Bravo AF: 0.0210

EpiCase AF: 0.000218

EpiControl AF: 0.000356

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Apr 20, 2018

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.68
Cadd	Benign	9.8
Dann	Benign	0.95

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: rs115372949; hg19: chr18-55103308;