Variant chr1-26950762-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

The NM_152365.3(KDF1):c.1040-6C>T variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00366 in 1,613,346 control chromosomes in the GnomAD database, including 11 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.0022 ( 1 hom., cov: 32)

Exomes 𝑓: 0.0038 ( 10 hom. )

Consequence

KDF1
NM_152365.3 splice_region, intron

Scores

Splicing: ADA: 0.00006681

Clinical Significance

Benign criteria provided, single submitter B:2

Conservation

PhyloP100: 0.583

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 -10 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.69).

BP6

Variant 1-26950762-G-A is Benign according to our data. Variant chr1-26950762-G-A is described in ClinVar as [Benign]. Clinvar id is 782077.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High AC in GnomAd4 at 340 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	MANE	Protein	UniProt
KDF1	NM_152365.3 linkuse as main transcript	c.1040-6C>T	splice_region_variant, intron_variant	ENST00000320567.6	NP_689578.2
KDF1	XM_005245735.3 linkuse as main transcript	c.1040-6C>T	splice_region_variant, intron_variant		XP_005245792.1	Q8NAX2
KDF1	XM_011540622.3 linkuse as main transcript	c.1040-6C>T	splice_region_variant, intron_variant		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.1040-6C>T		splice_region_variant, intron_variant		2	NM_152365.3	ENSP00000319179.5		Q8NAX2

Frequencies

GnomAD3 genomes

AF:

0.00223

AC:

340

AN:

152194

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00125

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00288

Gnomad ASJ

AF:

0.000576

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.0000942

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00348

Gnomad OTH

AF:

0.00191

GnomAD3 exomes

AF:

0.00188

AC:

472

AN:

251278

Hom.:

AF XY:

0.00186

AC XY:

253

AN XY:

135790

show subpopulations

Gnomad AFR exome

AF:

0.000862

Gnomad AMR exome

AF:

0.000984

Gnomad ASJ exome

AF:

0.000795

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000196

Gnomad FIN exome

AF:

0.000324

Gnomad NFE exome

AF:

0.00344

Gnomad OTH exome

AF:

0.00196

GnomAD4 exome

AF:

0.00380

AC:

5558

AN:

1461034

Hom.:

Cov.:

AF XY:

0.00359

AC XY:

2607

AN XY:

726908

show subpopulations

Gnomad4 AFR exome

AF:

0.000598

Gnomad4 AMR exome

AF:

0.000962

Gnomad4 ASJ exome

AF:

0.000536

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000301

Gnomad4 FIN exome

AF:

0.000281

Gnomad4 NFE exome

AF:

0.00470

Gnomad4 OTH exome

AF:

0.00356

GnomAD4 genome

AF:

0.00223

AC:

340

AN:

152312

Hom.:

Cov.:

AF XY:

0.00200

AC XY:

149

AN XY:

74486

show subpopulations

Gnomad4 AFR

AF:

0.00125

Gnomad4 AMR

AF:

0.00288

Gnomad4 ASJ

AF:

0.000576

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.0000942

Gnomad4 NFE

AF:

0.00348

Gnomad4 OTH

AF:

0.00189

Alfa

AF:

0.00299

Hom.:

Bravo

AF:

0.00246

Asia WGS

AF:

0.000866

AC:

AN:

3478

EpiCase

AF:

0.00349

EpiControl

AF:

0.00409

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

KDF1-related disorder

Benign:1

Likely benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Dec 09, 2019

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

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Nov 16, 2023

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.69

CADD

Benign

7.4

DANN

Benign

0.78

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.000067

dbscSNV1_RF

Benign

0.014

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