Variant 12-52544690-C-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_033448.3(KRT71):c.1414G>T(p.Val472Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0055 in 1,613,508 control chromosomes in the GnomAD database, including 33 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0040 ( 2 hom., cov: 33)

Exomes 𝑓: 0.0057 ( 31 hom. )

Consequence

KRT71
NM_033448.3 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:2

Conservation

PhyloP100: 1.61

Variant links:

Genes affected

KRT71 (HGNC:28927): (keratin 71) Keratins are intermediate filament proteins responsible for the structural integrity of epithelial cells and are subdivided into epithelial keratins and hair keratins. This gene encodes a protein that is expressed in the inner root sheath of hair follicles. The type II keratins are clustered in a region of chromosome 12q13.[provided by RefSeq, Jun 2009]

KRT71 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 (MetaRNN=0.0070506036).

BP6

Variant 12-52544690-C-A is Benign according to our data. Variant chr12-52544690-C-A is described in ClinVar as [Likely_benign]. Clinvar id is 771895.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High AC in GnomAd4 at 609 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
KRT71	NM_033448.3 linkuse as main transcript	c.1414G>T	p.Val472Phe	missense_variant	9/9	ENST00000267119.6	NP_258259.1
KRT71	XM_047428197.1 linkuse as main transcript	c.1288G>T	p.Val430Phe	missense_variant	8/8		XP_047284153.1
KRT71	XM_017018749.2 linkuse as main transcript	c.1168G>T	p.Val390Phe	missense_variant	10/10		XP_016874238.1
KRT71	XM_047428196.1 linkuse as main transcript	c.1030-341G>T		intron_variant			XP_047284152.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
KRT71	ENST00000267119.6 linkuse as main transcript	c.1414G>T	p.Val472Phe	missense_variant	9/9	1	NM_033448.3	ENSP00000267119	P1

Frequencies

GnomAD3 genomes

AF:

0.00400

AC:

608

AN:

152174

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00138

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00406

Gnomad ASJ

AF:

0.000288

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000414

Gnomad FIN

AF:

0.00179

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00670

Gnomad OTH

AF:

0.00526

GnomAD3 exomes

AF:

0.00396

AC:

988

AN:

249220

Hom.:

AF XY:

0.00385

AC XY:

520

AN XY:

135004

show subpopulations

Gnomad AFR exome

AF:

0.00106

Gnomad AMR exome

AF:

0.00272

Gnomad ASJ exome

AF:

0.000897

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000163

Gnomad FIN exome

AF:

0.00226

Gnomad NFE exome

AF:

0.00693

Gnomad OTH exome

AF:

0.00592

GnomAD4 exome

AF:

0.00566

AC:

8264

AN:

1461216

Hom.:

Cov.:

AF XY:

0.00546

AC XY:

3970

AN XY:

726928

show subpopulations

Gnomad4 AFR exome

AF:

0.000866

Gnomad4 AMR exome

AF:

0.00291

Gnomad4 ASJ exome

AF:

0.000842

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000185

Gnomad4 FIN exome

AF:

0.00274

Gnomad4 NFE exome

AF:

0.00682

Gnomad4 OTH exome

AF:

0.00530

GnomAD4 genome

AF:

0.00400

AC:

609

AN:

152292

Hom.:

Cov.:

AF XY:

0.00379

AC XY:

282

AN XY:

74460

show subpopulations

Gnomad4 AFR

AF:

0.00137

Gnomad4 AMR

AF:

0.00405

Gnomad4 ASJ

AF:

0.000288

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000621

Gnomad4 FIN

AF:

0.00179

Gnomad4 NFE

AF:

0.00670

Gnomad4 OTH

AF:

0.00520

Alfa

AF:

0.00583

Hom.:

Bravo

AF:

0.00414

TwinsUK

AF:

0.00512

AC:

ALSPAC

AF:

0.00727

AC:

ESP6500AA

AF:

0.00113

AC:

ESP6500EA

AF:

0.00523

AC:

ExAC

AF:

0.00418

AC:

507

Asia WGS

AF:

0.000577

AC:

AN:

3478

EpiCase

AF:

0.00671

EpiControl

AF:

0.00587

ClinVar

Significance: Likely benign

Submissions summary: Benign:2

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

KRT71-related disorder

Benign:1

Benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Jul 30, 2019

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

not provided

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Jan 04, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.098

BayesDel_addAF

Benign

-0.20

BayesDel_noAF

Uncertain

-0.050

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.036

Eigen

Benign

-0.068

Eigen_PC

Benign

-0.026

FATHMM_MKL

Uncertain

0.82

LIST_S2

Benign

0.77

M_CAP

Uncertain

0.11

MetaRNN

Benign

0.0071

MetaSVM

Benign

-0.55

MutationAssessor

Uncertain

2.3

MutationTaster

Benign

0.50

PrimateAI

Uncertain

0.52

PROVEAN

Benign

-0.29

REVEL

Uncertain

0.40

Sift

Benign

0.17

Sift4G

Benign

0.70

Polyphen

0.91

Vest4

0.39

MVP

0.69

MPC

0.32

ClinPred

0.028

GERP RS

4.2

Varity_R

0.22

gMVP

0.57

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