Variant 17-40698312-A-G 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 ENST00000264651.3(KRT24):c.1503T>C(p.Thr501Thr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00186 in 1,612,430 control chromosomes in the GnomAD database, including 45 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0082 ( 15 hom., cov: 32)

Exomes 𝑓: 0.0012 ( 30 hom. )

Consequence

KRT24
ENST00000264651.3 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 0.688

Variant links:

Genes affected

KRT24 (HGNC:18527): (keratin 24) This gene encodes a member of the type I (acidic) keratin family, which belongs to the superfamily of intermediate filament (IF) proteins. Keratins are heteropolymeric structural proteins which form the intermediate filament. These filaments, along with actin microfilaments and microtubules, compose the cytoskeleton of epithelial cells. The type I keratin genes are clustered in a region of chromosome 17q12-q21. [provided by RefSeq, Jun 2009]

KRT24 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=-0.62).

BP6

Variant 17-40698312-A-G is Benign according to our data. Variant chr17-40698312-A-G is described in ClinVar as [Benign]. Clinvar id is 710111.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=0.688 with no splicing effect.

BS1

Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00822 (1251/152260) while in subpopulation AFR AF= 0.0272 (1130/41536). AF 95% confidence interval is 0.0259. There are 15 homozygotes in gnomad4. There are 559 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 15 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
KRT24	NM_019016.3 linkuse as main transcript	c.1503T>C	p.Thr501Thr	synonymous_variant	8/8	ENST00000264651.3	NP_061889.2	Q2M2I5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
KRT24	ENST00000264651.3 linkuse as main transcript	c.1503T>C	p.Thr501Thr	synonymous_variant	8/8	1	NM_019016.3	ENSP00000264651.2		Q2M2I5

Frequencies

GnomAD3 genomes

AF:

0.00818

AC:

1245

AN:

152142

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0271

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00439

Gnomad ASJ

AF:

0.000288

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.0127

Gnomad NFE

AF:

0.000529

Gnomad OTH

AF:

0.00670

GnomAD3 exomes

AF:

0.00243

AC:

608

AN:

249854

Hom.:

AF XY:

0.00160

AC XY:

217

AN XY:

135212

show subpopulations

Gnomad AFR exome

AF:

0.0281

Gnomad AMR exome

AF:

0.00240

Gnomad ASJ exome

AF:

0.000397

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000982

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000410

Gnomad OTH exome

AF:

0.00245

GnomAD4 exome

AF:

0.00120

AC:

1753

AN:

1460170

Hom.:

Cov.:

AF XY:

0.00113

AC XY:

820

AN XY:

726506

show subpopulations

Gnomad4 AFR exome

AF:

0.0333

Gnomad4 AMR exome

AF:

0.00306

Gnomad4 ASJ exome

AF:

0.000268

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000116

Gnomad4 FIN exome

AF:

0.0000187

Gnomad4 NFE exome

AF:

0.000230

Gnomad4 OTH exome

AF:

0.00300

GnomAD4 genome

AF:

0.00822

AC:

1251

AN:

152260

Hom.:

Cov.:

AF XY:

0.00751

AC XY:

559

AN XY:

74436

show subpopulations

Gnomad4 AFR

AF:

0.0272

Gnomad4 AMR

AF:

0.00438

Gnomad4 ASJ

AF:

0.000288

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000529

Gnomad4 OTH

AF:

0.00663

Alfa

AF:

0.00417

Hom.:

Bravo

AF:

0.00949

Asia WGS

AF:

0.00260

AC:

AN:

3478

EpiCase

AF:

0.000928

EpiControl

AF:

0.000474

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Aug 15, 2017	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.62

CADD

Benign

5.9

DANN

Benign

0.47

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