Variant 1-26951532-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BS1BS2

The NM_152365.3(KDF1):c.849G>A(p.Thr283Thr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0342 in 1,612,838 control chromosomes in the GnomAD database, including 1,128 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.025 ( 62 hom., cov: 32)

Exomes 𝑓: 0.035 ( 1066 hom. )

Consequence

KDF1
NM_152365.3 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: -1.55

Variant links:

Genes affected

KDF1 (HGNC:26624): (keratinocyte differentiation factor 1) Predicted to be involved in several processes, including positive regulation of epidermal cell differentiation; regulation of epidermal cell division; and skin development. Predicted to act upstream of or within keratinocyte development and negative regulation of keratinocyte proliferation. Located in cell junction; mitotic spindle; and nucleoplasm. Implicated in ectodermal dysplasia 12. [provided by Alliance of Genome Resources, Apr 2022]

KDF1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.67).

BP6

Variant 1-26951532-C-T is Benign according to our data. Variant chr1-26951532-C-T is described in ClinVar as [Benign]. Clinvar id is 1594784.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-1.55 with no splicing effect.

BS1

Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.0246 (3748/152300) while in subpopulation NFE AF= 0.039 (2653/68016). AF 95% confidence interval is 0.0378. There are 62 homozygotes in gnomad4. There are 1793 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High AC in GnomAd4 at 3748 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
KDF1	NM_152365.3 linkuse as main transcript	c.849G>A	p.Thr283Thr	synonymous_variant	2/4	ENST00000320567.6	NP_689578.2
KDF1	XM_005245735.3 linkuse as main transcript	c.849G>A	p.Thr283Thr	synonymous_variant	2/4		XP_005245792.1	Q8NAX2
KDF1	XM_011540622.3 linkuse as main transcript	c.849G>A	p.Thr283Thr	synonymous_variant	2/4		XP_011538924.1	Q8NAX2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
KDF1	ENST00000320567.6 linkuse as main transcript	c.849G>A	p.Thr283Thr	synonymous_variant	2/4	2	NM_152365.3	ENSP00000319179.5		Q8NAX2

Frequencies

GnomAD3 genomes

AF:

0.0246

AC:

3748

AN:

152182

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00741

Gnomad AMI

AF:

0.0110

Gnomad AMR

AF:

0.0166

Gnomad ASJ

AF:

0.0213

Gnomad EAS

AF:

0.000192

Gnomad SAS

AF:

0.00518

Gnomad FIN

AF:

0.0359

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.0390

Gnomad OTH

AF:

0.0206

GnomAD3 exomes

AF:

0.0242

AC:

6072

AN:

251172

Hom.:

106

AF XY:

0.0242

AC XY:

3281

AN XY:

135808

show subpopulations

Gnomad AFR exome

AF:

0.00634

Gnomad AMR exome

AF:

0.0103

Gnomad ASJ exome

AF:

0.0221

Gnomad EAS exome

AF:

0.000109

Gnomad SAS exome

AF:

0.00529

Gnomad FIN exome

AF:

0.0326

Gnomad NFE exome

AF:

0.0385

Gnomad OTH exome

AF:

0.0245

GnomAD4 exome

AF:

0.0352

AC:

51340

AN:

1460538

Hom.:

1066

Cov.:

AF XY:

0.0341

AC XY:

24754

AN XY:

726258

show subpopulations

Gnomad4 AFR exome

AF:

0.00529

Gnomad4 AMR exome

AF:

0.0107

Gnomad4 ASJ exome

AF:

0.0232

Gnomad4 EAS exome

AF:

0.0000757

Gnomad4 SAS exome

AF:

0.00523

Gnomad4 FIN exome

AF:

0.0355

Gnomad4 NFE exome

AF:

0.0413

Gnomad4 OTH exome

AF:

0.0306

GnomAD4 genome

AF:

0.0246

AC:

3748

AN:

152300

Hom.:

Cov.:

AF XY:

0.0241

AC XY:

1793

AN XY:

74454

show subpopulations

Gnomad4 AFR

AF:

0.00738

Gnomad4 AMR

AF:

0.0165

Gnomad4 ASJ

AF:

0.0213

Gnomad4 EAS

AF:

0.000193

Gnomad4 SAS

AF:

0.00518

Gnomad4 FIN

AF:

0.0359

Gnomad4 NFE

AF:

0.0390

Gnomad4 OTH

AF:

0.0203

Alfa

AF:

0.0344

Hom.:

Bravo

AF:

0.0222

Asia WGS

AF:

0.00346

AC:

AN:

3478

EpiCase

AF:

0.0359

EpiControl

AF:

0.0353

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 24, 2024	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

KDF1-related disorder

Benign:1

Benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Aug 14, 2019

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.67

CADD

Benign

5.8

DANN

Benign

0.83

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over