1-44140033-T-C

Position:

• chr1-44140033-T-C

Variant summary

Our verdict is Benign. Variant got -7 ACMG points: 0P and 7B. BP4_Strong BP6_Moderate BP7

The NM_001358438.1(KLF18):​c.1599A>G​(p.Thr533=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00229 in 106,544 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0023 (0 hom., cov: 22)
  • Exomes 𝑓: 0.00052 (5 hom.)
  • Failed GnomAD Quality Control
• Consequence: KLF18 NM_001358438.1 synonymous
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -3.98

Genes affected

KLF18 (HGNC:51793): (KLF transcription factor 18) Predicted to enable DNA-binding transcription factor activity, RNA polymerase II-specific and RNA polymerase II cis-regulatory region sequence-specific DNA binding activity. Predicted to be involved in regulation of transcription by RNA polymerase II. Predicted to be located in nucleus. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Benign. Variant got -7 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BP6: Variant 1-44140033-T-C is Benign according to our data. Variant chr1-44140033-T-C is described in ClinVar as [Likely_benign]. Clinvar id is 2638769.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=-3.98 with no splicing effect.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
KLF18	NM_001358438.1	c.1599A>G	p.Thr533=	synonymous_variant	1/2	ENST00000634670.1	NP_001345367.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
KLF18	ENST00000634670.1	c.1599A>G	p.Thr533=	synonymous_variant	1/2	5	NM_001358438.1	ENSP00000489024	P1

Frequencies

GnomAD3 genomes AF: 0.00227 AC: 242 AN: 106458 Hom.: 0 Cov.: 22

Gnomad AFR AF: 0.00524

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00265

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00487

Gnomad SAS AF: 0.000688

Gnomad FIN AF: 0.00247

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000745

Gnomad OTH AF: 0.00203

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.000523 AC: 113 AN: 216220 Hom.: 5 Cov.: 0 AF XY: 0.000517 AC XY: 57 AN XY: 110286

Gnomad4 AFR exome AF: 0.00632

Gnomad4 AMR exome AF: 0.00123

Gnomad4 ASJ exome AF: 0.000125

Gnomad4 EAS exome AF: 0.00165

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.000160

Gnomad4 NFE exome AF: 0.000163

Gnomad4 OTH exome AF: 0.000702

GnomAD4 genome AF: 0.00229 AC: 244 AN: 106544 Hom.: 0 Cov.: 22 AF XY: 0.00240 AC XY: 125 AN XY: 51986

Gnomad4 AFR AF: 0.00530

Gnomad4 AMR AF: 0.00264

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00488

Gnomad4 SAS AF: 0.000690

Gnomad4 FIN AF: 0.00247

Gnomad4 NFE AF: 0.000745

Gnomad4 OTH AF: 0.00201

Alfa AF: 0.00986 Hom.: 0

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Feb 01, 2023

KLF18: BP4, BP7 -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.65
DANN	Benign	0.39

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: rs376727707; hg19: chr1-44605705;