Variant 12-52567100-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_StrongBA1

The NM_175053.4(KRT74):c.1459G>A(p.Ala487Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0463 in 1,603,648 control chromosomes in the GnomAD database, including 2,041 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.035 ( 133 hom., cov: 32)

Exomes 𝑓: 0.048 ( 1908 hom. )

Consequence

KRT74
NM_175053.4 missense

Scores

Clinical Significance

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

Conservation

PhyloP100: -0.440

Variant links:

Genes affected

KRT74 (HGNC:28929): (keratin 74) Keratins are intermediate filament proteins responsible for the structural integrity of epithelial cells and are subdivided into epithelial keratins and hair keratins. This protein belongs to a family of keratins that are specifically expressed in the inner root sheath of hair follicles.[provided by RefSeq, Jun 2009]

KRT74 links:

KRT74 (HGNC:):

KRT74 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=0.0018889904).

BP6

Variant 12-52567100-C-T is Benign according to our data. Variant chr12-52567100-C-T is described in ClinVar as [Benign]. Clinvar id is 1655951.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0504 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
KRT74	NM_175053.4 linkuse as main transcript	c.1459G>A	p.Ala487Thr	missense_variant	9/9	ENST00000305620.3	NP_778223.2	Q7RTS7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
KRT74	ENST00000305620.3 linkuse as main transcript	c.1459G>A	p.Ala487Thr	missense_variant	9/9	1	NM_175053.4	ENSP00000307240.2	Q7RTS7
KRT74	ENST00000549343.5 linkuse as main transcript	c.1501G>A	p.Ala501Thr	missense_variant	10/10	5		ENSP00000447447.1	F8W1S1
KRT74	ENST00000546384.1 linkuse as main transcript	n.446G>A		non_coding_transcript_exon_variant	3/3	4

Frequencies

GnomAD3 genomes

AF:

0.0347

AC:

5282

AN:

152048

Hom.:

133

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00961

Gnomad AMI

AF:

0.0866

Gnomad AMR

AF:

0.0288

Gnomad ASJ

AF:

0.0484

Gnomad EAS

AF:

0.000193

Gnomad SAS

AF:

0.00727

Gnomad FIN

AF:

0.0516

Gnomad MID

AF:

0.0506

Gnomad NFE

AF:

0.0519

Gnomad OTH

AF:

0.0345

GnomAD3 exomes

AF:

0.0331

AC:

8168

AN:

247088

Hom.:

197

AF XY:

0.0333

AC XY:

4454

AN XY:

133704

show subpopulations

Gnomad AFR exome

AF:

0.00853

Gnomad AMR exome

AF:

0.0234

Gnomad ASJ exome

AF:

0.0430

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00706

Gnomad FIN exome

AF:

0.0483

Gnomad NFE exome

AF:

0.0478

Gnomad OTH exome

AF:

0.0446

GnomAD4 exome

AF:

0.0475

AC:

68965

AN:

1451484

Hom.:

1908

Cov.:

AF XY:

0.0463

AC XY:

33337

AN XY:

719846

show subpopulations

Gnomad4 AFR exome

AF:

0.00720

Gnomad4 AMR exome

AF:

0.0250

Gnomad4 ASJ exome

AF:

0.0446

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00753

Gnomad4 FIN exome

AF:

0.0482

Gnomad4 NFE exome

AF:

0.0546

Gnomad4 OTH exome

AF:

0.0470

GnomAD4 genome

AF:

0.0347

AC:

5277

AN:

152164

Hom.:

133

Cov.:

AF XY:

0.0335

AC XY:

2491

AN XY:

74380

show subpopulations

Gnomad4 AFR

AF:

0.00958

Gnomad4 AMR

AF:

0.0288

Gnomad4 ASJ

AF:

0.0484

Gnomad4 EAS

AF:

0.000194

Gnomad4 SAS

AF:

0.00707

Gnomad4 FIN

AF:

0.0516

Gnomad4 NFE

AF:

0.0518

Gnomad4 OTH

AF:

0.0342

Alfa

AF:

0.0462

Hom.:

306

Bravo

AF:

0.0324

TwinsUK

AF:

0.0450

AC:

167

ALSPAC

AF:

0.0540

AC:

208

ESP6500AA

AF:

0.00862

AC:

ESP6500EA

AF:

0.0522

AC:

449

ExAC

AF:

0.0312

AC:

3786

Asia WGS

AF:

0.00924

AC:

AN:

3478

EpiCase

AF:

0.0557

EpiControl

AF:

0.0529

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	Jan 05, 2024	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.066

BayesDel_addAF

Benign

-0.58

BayesDel_noAF

Benign

-0.57

CADD

Benign

0.24

DANN

Benign

0.71

DEOGEN2

Benign

0.014

T;T

Eigen

Benign

-2.0

Eigen_PC

Benign

-2.0

FATHMM_MKL

Benign

0.00049

LIST_S2

Benign

0.17

T;T

MetaRNN

Benign

0.0019

T;T

MetaSVM

Benign

-0.94

MutationAssessor

Benign

0.0

.;N

PrimateAI

Benign

0.25

PROVEAN

Benign

-0.77

N;N

REVEL

Benign

0.18

Sift

Benign

0.63

T;T

Sift4G

Benign

0.26

T;T

Polyphen

0.0

.;B

Vest4

0.031

MPC

0.063

ClinPred

0.0056

GERP RS

-8.1

Varity_R

0.024

gMVP

0.088

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