chr12-52233347-C-A

Variant names:

Variant summary

Our verdict is Benign. The variant received -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. 14/21 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

Publications

2 publications found

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 was made for transcript

Our verdict: Benign. The variant received -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 VariationId 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. GnomAdExome4 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 GnomAdExome4. There are 943 alleles in the male GnomAdExome4 subpopulation. Median coverage is 31. This position passed quality control check.

BS2

High Homozygotes in GnomAd4 at 8 AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_005556.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KRT7	NM_005556.4	MANE Select	c.51C>A	p.Phe17Leu	missense	Exon 1 of 9	NP_005547.3

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
KRT7	ENST00000331817.6	TSL:1 MANE Select	c.51C>A	p.Phe17Leu	missense	Exon 1 of 9	ENSP00000329243.5	P08729
KRT7	ENST00000955643.1		c.51C>A	p.Phe17Leu	missense	Exon 1 of 10	ENSP00000625702.1
KRT7	ENST00000955640.1		c.51C>A	p.Phe17Leu	missense	Exon 1 of 10	ENSP00000625699.1

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

GnomAD2 exomes

AF:

0.00639

AC:

1241

AN:

194104

AF XY:

0.00499

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 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

African (AFR)

AF:

0.0000692

AC:

AN:

28906

American (AMR)

AF:

0.0228

AC:

867

AN:

38008

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

24644

East Asian (EAS)

AF:

0.0119

AC:

403

AN:

33968

South Asian (SAS)

AF:

0.000306

AC:

AN:

81688

European-Finnish (FIN)

AF:

0.0110

AC:

576

AN:

52144

Middle Eastern (MID)

AF:

0.000177

AC:

AN:

5634

European-Non Finnish (NFE)

AF:

0.000140

AC:

154

AN:

1096440

Other (OTH)

AF:

0.00192

AC:

112

AN:

58460

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.485

Heterozygous variant carriers

116

232

349

465

581

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

112

140

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.00222

AC:

338

AN:

152300

Hom.:

Cov.:

AF XY:

0.00242

AC XY:

180

AN XY:

74468

show subpopulations

African (AFR)

AF:

0.000337

AC:

AN:

41578

American (AMR)

AF:

0.00823

AC:

126

AN:

15304

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.0142

AC:

AN:

5154

South Asian (SAS)

AF:

0.000207

AC:

AN:

4834

European-Finnish (FIN)

AF:

0.00829

AC:

AN:

10620

Middle Eastern (MID)

AF:

0.00342

AC:

AN:

292

European-Non Finnish (NFE)

AF:

0.000456

AC:

AN:

68018

Other (OTH)

AF:

0.00189

AC:

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.492

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.00132

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

ClinVar submissions

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (2)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Uncertain

0.38

BayesDel_addAF

Benign

-0.36

BayesDel_noAF

Benign

-0.27

CADD

Benign

7.0

(source)

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

PhyloP100

0.57

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

PromoterAI

-0.030

Neutral

(source)

Varity_R

0.037

gMVP

0.36

Mutation Taster

=89/11

polymorphism

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over