Variant 17-40699561-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_019016.3(KRT24):c.1244G>A(p.Cys415Tyr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00158 in 1,614,112 control chromosomes in the GnomAD database, including 40 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

Frequency

Genomes: 𝑓 0.0078 ( 15 hom., cov: 32)

Exomes 𝑓: 0.00092 ( 25 hom. )

Consequence

KRT24
NM_019016.3 missense

Scores

Clinical Significance

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

Conservation

PhyloP100: -0.791

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 -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.005050212).

BP6

Variant 17-40699561-C-T is Benign according to our data. Variant chr17-40699561-C-T is described in ClinVar as [Benign]. Clinvar id is 710113.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00784 (1194/152276) while in subpopulation AFR AF= 0.027 (1123/41542). AF 95% confidence interval is 0.0257. There are 15 homozygotes in gnomad4. There are 532 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.1244G>A	p.Cys415Tyr	missense_variant	6/8	ENST00000264651.3	NP_061889.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
KRT24	ENST00000264651.3 linkuse as main transcript	c.1244G>A	p.Cys415Tyr	missense_variant	6/8	1	NM_019016.3	ENSP00000264651	P1

Frequencies

GnomAD3 genomes

AF:

0.00781

AC:

1188

AN:

152158

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0270

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00327

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.000162

Gnomad OTH

AF:

0.00430

GnomAD3 exomes

AF:

0.00202

AC:

507

AN:

251450

Hom.:

AF XY:

0.00124

AC XY:

169

AN XY:

135896

show subpopulations

Gnomad AFR exome

AF:

0.0280

Gnomad AMR exome

AF:

0.00119

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000327

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000440

Gnomad OTH exome

AF:

0.000814

GnomAD4 exome

AF:

0.000924

AC:

1351

AN:

1461836

Hom.:

Cov.:

AF XY:

0.000820

AC XY:

596

AN XY:

727216

show subpopulations

Gnomad4 AFR exome

AF:

0.0326

Gnomad4 AMR exome

AF:

0.00174

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000232

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000288

Gnomad4 OTH exome

AF:

0.00220

GnomAD4 genome

AF:

0.00784

AC:

1194

AN:

152276

Hom.:

Cov.:

AF XY:

0.00714

AC XY:

532

AN XY:

74468

show subpopulations

Gnomad4 AFR

AF:

0.0270

Gnomad4 AMR

AF:

0.00327

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000162

Gnomad4 OTH

AF:

0.00426

Alfa

AF:

0.00144

Hom.:

Bravo

AF:

0.00898

ESP6500AA

AF:

0.0256

AC:

113

ESP6500EA

AF:

0.000233

AC:

ExAC

AF:

0.00246

AC:

299

Asia WGS

AF:

0.00231

AC:

AN:

3478

EpiCase

AF:

0.0000545

EpiControl

AF:

0.000119

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

AlphaMissense

Benign

0.13

BayesDel_addAF

Benign

-0.41

BayesDel_noAF

Benign

-0.34

CADD

Benign

DANN

Benign

0.85

DEOGEN2

Benign

0.18

Eigen

Benign

-0.25

Eigen_PC

Benign

-0.20

FATHMM_MKL

Benign

0.26

LIST_S2

Benign

0.32

MetaRNN

Benign

0.0051

MetaSVM

Benign

-0.68

MutationAssessor

Benign

1.4

MutationTaster

Benign

0.97

PrimateAI

Benign

0.38

PROVEAN

Uncertain

-2.9

REVEL

Benign

0.27

Sift

Benign

1.0

Sift4G

Benign

0.34

Polyphen

0.51

Vest4

0.32

MVP

0.33

MPC

0.49

ClinPred

0.029

GERP RS

4.6

Varity_R

0.23

gMVP

0.30

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.030

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