chr12-52233347-C-A

Variant names:

Variant summary

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

The NM_005556.4(KRT7):c.51C>A(p.Phe17Leu) 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 1,572,192 control chromosomes in the GnomAD database, including 28 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0022 ( 8 hom., cov: 33)

Exomes 𝑓: 0.0015 ( 20 hom. )

Consequence

KRT7
NM_005556.4 missense

Scores

Clinical Significance

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

Conservation

PhyloP100: 0.566

Variant links:

Genes affected

KRT7 (HGNC:6445): (keratin 7) The protein encoded by this gene is a member of the keratin gene family. The type II cytokeratins consist of basic or neutral proteins which are arranged in pairs of heterotypic keratin chains coexpressed during differentiation of simple and stratified epithelial tissues. This type II cytokeratin is specifically expressed in the simple epithelia lining the cavities of the internal organs and in the gland ducts and blood vessels. The genes encoding the type II cytokeratins are clustered in a region of chromosome 12q12-q13. Alternative splicing may result in several transcript variants; however, not all variants have been fully described. [provided by RefSeq, Jul 2008]

KRT7 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0022589564).

BP6

Variant 12-52233347-C-A is Benign according to our data. Variant chr12-52233347-C-A is described in ClinVar as [Benign]. Clinvar id is 769820.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population amr. gnomad4_exome allele frequency = 0.00151 (2140/1419892) while in subpopulation AMR AF= 0.0228 (867/38008). AF 95% confidence interval is 0.0216. There are 20 homozygotes in gnomad4_exome. There are 943 alleles in male gnomad4_exome subpopulation. Median coverage is 31. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 8 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
KRT7	NM_005556.4 link	c.51C>A	p.Phe17Leu	missense_variant	Exon 1 of 9	ENST00000331817.6	NP_005547.3	P08729
KRT7	XM_011538325.3 link	c.51C>A	p.Phe17Leu	missense_variant	Exon 1 of 8		XP_011536627.1
KRT7	XM_047428827.1 link	c.51C>A	p.Phe17Leu	missense_variant	Exon 1 of 7		XP_047284783.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
KRT7	ENST00000331817.6 link	c.51C>A	p.Phe17Leu	missense_variant	Exon 1 of 9	1	NM_005556.4	ENSP00000329243.5		P08729
KRT7	ENST00000546666.1 link	n.199C>A		non_coding_transcript_exon_variant	Exon 2 of 2	4

Frequencies

GnomAD3 genomes

AF:

0.00221

AC:

336

AN:

152188

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000338

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00811

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.0141

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.00829

Gnomad MID

AF:

0.00318

Gnomad NFE

AF:

0.000456

Gnomad OTH

AF:

0.00191

GnomAD3 exomes

AF:

0.00639

AC:

1241

AN:

194104

Hom.:

AF XY:

0.00499

AC XY:

541

AN XY:

108516

show subpopulations

Gnomad AFR exome

AF:

0.000324

Gnomad AMR exome

AF:

0.0266

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0154

Gnomad SAS exome

AF:

0.000195

Gnomad FIN exome

AF:

0.0114

Gnomad NFE exome

AF:

0.000667

Gnomad OTH exome

AF:

0.00874

GnomAD4 exome

AF:

0.00151

AC:

2140

AN:

1419892

Hom.:

Cov.:

AF XY:

0.00134

AC XY:

943

AN XY:

706200

show subpopulations

Gnomad4 AFR exome

AF:

0.0000692

Gnomad4 AMR exome

AF:

0.0228

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0119

Gnomad4 SAS exome

AF:

0.000306

Gnomad4 FIN exome

AF:

0.0110

Gnomad4 NFE exome

AF:

0.000140

Gnomad4 OTH exome

AF:

0.00192

GnomAD4 genome

AF:

0.00222

AC:

338

AN:

152300

Hom.:

Cov.:

AF XY:

0.00242

AC XY:

180

AN XY:

74468

show subpopulations

Gnomad4 AFR

AF:

0.000337

Gnomad4 AMR

AF:

0.00823

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.0142

Gnomad4 SAS

AF:

0.000207

Gnomad4 FIN

AF:

0.00829

Gnomad4 NFE

AF:

0.000456

Gnomad4 OTH

AF:

0.00189

Alfa

AF:

0.00108

Hom.:

Bravo

AF:

0.00297

ESP6500AA

AF:

0.000456

AC:

ESP6500EA

AF:

0.000465

AC:

ExAC

AF:

0.00505

AC:

609

Asia WGS

AF:

0.00260

AC:

AN:

3472

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Jun 22, 2018

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Uncertain

0.38

BayesDel_addAF

Benign

-0.36

BayesDel_noAF

Benign

-0.27

CADD

Benign

7.0

DANN

Benign

0.62

DEOGEN2

Benign

0.083

Eigen

Benign

-1.6

Eigen_PC

Benign

-1.6

FATHMM_MKL

Benign

0.098

LIST_S2

Benign

0.31

MetaRNN

Benign

0.0023

MetaSVM

Benign

-0.96

MutationAssessor

Benign

1.5

PrimateAI

Uncertain

0.58

PROVEAN

Benign

-1.2

REVEL

Benign

0.29

Sift

Benign

0.61

Sift4G

Benign

0.46

Polyphen

0.0

Vest4

0.037

MutPred

0.21

Gain of MoRF binding (P = 0.0951);

MVP

0.18

MPC

0.32

ClinPred

0.0034

GERP RS

-0.85

Varity_R

0.037

gMVP

0.36

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