Variant rs11170177 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.495C>G(p.Asn165Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0619 in 1,613,830 control chromosomes in the GnomAD database, including 4,760 homozygotes. In-silico tool predicts 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 0.050 ( 411 hom., cov: 32)

Exomes 𝑓: 0.063 ( 4349 hom. )

Consequence

KRT74
NM_175053.4 missense

Scores

Clinical Significance

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

Conservation

PhyloP100: 3.08

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:

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=0.0017719865).

BP6

Variant 12-52572644-G-C is Benign according to our data. Variant chr12-52572644-G-C is described in ClinVar as [Benign]. Clinvar id is 1289755.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.293 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.495C>G	p.Asn165Lys	missense_variant	2/9	ENST00000305620.3	NP_778223.2	Q7RTS7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
KRT74	ENST00000305620.3 linkuse as main transcript	c.495C>G	p.Asn165Lys	missense_variant	2/9	1	NM_175053.4	ENSP00000307240.2		Q7RTS7
KRT74	ENST00000549343.5 linkuse as main transcript	c.495C>G	p.Asn165Lys	missense_variant	2/10	5		ENSP00000447447.1		F8W1S1

Frequencies

GnomAD3 genomes

AF:

0.0501

AC:

7625

AN:

152124

Hom.:

411

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0110

Gnomad AMI

AF:

0.0615

Gnomad AMR

AF:

0.0307

Gnomad ASJ

AF:

0.0844

Gnomad EAS

AF:

0.306

Gnomad SAS

AF:

0.0806

Gnomad FIN

AF:

0.0398

Gnomad MID

AF:

0.0759

Gnomad NFE

AF:

0.0562

Gnomad OTH

AF:

0.0526

GnomAD3 exomes

AF:

0.0698

AC:

17561

AN:

251432

Hom.:

1218

AF XY:

0.0716

AC XY:

9727

AN XY:

135902

show subpopulations

Gnomad AFR exome

AF:

0.0103

Gnomad AMR exome

AF:

0.0355

Gnomad ASJ exome

AF:

0.0820

Gnomad EAS exome

AF:

0.303

Gnomad SAS exome

AF:

0.0773

Gnomad FIN exome

AF:

0.0408

Gnomad NFE exome

AF:

0.0543

Gnomad OTH exome

AF:

0.0585

GnomAD4 exome

AF:

0.0631

AC:

92269

AN:

1461588

Hom.:

4349

Cov.:

AF XY:

0.0638

AC XY:

46392

AN XY:

727116

show subpopulations

Gnomad4 AFR exome

AF:

0.00825

Gnomad4 AMR exome

AF:

0.0344

Gnomad4 ASJ exome

AF:

0.0835

Gnomad4 EAS exome

AF:

0.300

Gnomad4 SAS exome

AF:

0.0774

Gnomad4 FIN exome

AF:

0.0409

Gnomad4 NFE exome

AF:

0.0568

Gnomad4 OTH exome

AF:

0.0686

GnomAD4 genome

AF:

0.0500

AC:

7619

AN:

152242

Hom.:

411

Cov.:

AF XY:

0.0508

AC XY:

3785

AN XY:

74438

show subpopulations

Gnomad4 AFR

AF:

0.0110

Gnomad4 AMR

AF:

0.0306

Gnomad4 ASJ

AF:

0.0844

Gnomad4 EAS

AF:

0.306

Gnomad4 SAS

AF:

0.0800

Gnomad4 FIN

AF:

0.0398

Gnomad4 NFE

AF:

0.0562

Gnomad4 OTH

AF:

0.0554

Alfa

AF:

0.0636

Hom.:

367

Bravo

AF:

0.0476

TwinsUK

AF:

0.0607

AC:

225

ALSPAC

AF:

0.0589

AC:

227

ESP6500AA

AF:

0.0136

AC:

ESP6500EA

AF:

0.0549

AC:

472

ExAC

AF:

0.0693

AC:

8409

Asia WGS

AF:

0.144

AC:

500

AN:

3478

EpiCase

AF:

0.0540

EpiControl

AF:

0.0557

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 22, 2024	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Jun 10, 2021	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.86

BayesDel_addAF

Benign

-0.22

BayesDel_noAF

Uncertain

0.060

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Uncertain

0.78

D;D

Eigen

Pathogenic

0.94

Eigen_PC

Pathogenic

0.78

FATHMM_MKL

Pathogenic

0.99

LIST_S2

Benign

0.80

T;T

MetaRNN

Benign

0.0018

T;T

MetaSVM

Benign

-1.9

MutationAssessor

Pathogenic

4.0

.;H

PrimateAI

Uncertain

0.63

PROVEAN

Pathogenic

-5.8

D;D

REVEL

Pathogenic

0.73

Sift

Pathogenic

0.0

D;D

Sift4G

Pathogenic

0.0

D;D

Polyphen

1.0

.;D

Vest4

0.35

MutPred

0.43

Gain of ubiquitination at N165 (P = 0.0258);Gain of ubiquitination at N165 (P = 0.0258);

MPC

0.42

ClinPred

0.067

GERP RS

3.8

Varity_R

0.91

gMVP

0.76

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