Genetic Variant KRT7:n.423T>C (chr12-52251970-T-C) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The ENST00000548657.5(KRT7):n.423T>C variant causes a non coding transcript exon change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.288 in 599,200 control chromosomes in the GnomAD database, including 26,867 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.27 ( 6190 hom., cov: 33)

Exomes 𝑓: 0.29 ( 20677 hom. )

Consequence

KRT7
ENST00000548657.5 non_coding_transcript_exon

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.140

Publications

8 publications found

Variant links:

COSMIC-nc: COSV57766439

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:

KRT86 (HGNC:6463): (keratin 86) This gene encodes a type II keratin protein, which heterodimerizes with type I keratins to form hair and nails. This gene is present in a cluster of related genes and pseudogenes on chromosome 12. Mutations in this gene have been observed in patients with the hair disease monilethrix. [provided by RefSeq, Feb 2016]

KRT86 links:

KRT87P (HGNC:):

KRT87P links:

KRT87P (HGNC:30198): (keratin 87, pseudogene) Located in extracellular space. [provided by Alliance of Genome Resources, Apr 2022]

KRT87P links:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.89).

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.328 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
KRT7	XM_011538325.3 link	c.*61T>C		3_prime_UTR_variant	Exon 8 of 8		XP_011536627.1
KRT87P	NR_146088.1 link	n.1243+57A>G		intron_variant	Intron 8 of 8

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	Protein
KRT7	ENST00000548657.5 link	n.423T>C	non_coding_transcript_exon_variant	Exon 3 of 3	3
KRT86	ENST00000553310.6 link	c.-5+2542T>C	intron_variant	Intron 1 of 2	4	ENSP00000452237.3
KRT87P	ENST00000529785.1 link	n.1602+57A>G	intron_variant	Intron 8 of 8	2
KRT87P	ENST00000534226.5 link	n.1288+57A>G	intron_variant	Intron 8 of 8	6

Frequencies

GnomAD3 genomes

AF:

0.273

AC:

41495

AN:

151924

Hom.:

6194

Cov.:

show subpopulations

Gnomad AFR

AF:

0.203

Gnomad AMI

AF:

0.343

Gnomad AMR

AF:

0.178

Gnomad ASJ

AF:

0.262

Gnomad EAS

AF:

0.140

Gnomad SAS

AF:

0.293

Gnomad FIN

AF:

0.370

Gnomad MID

AF:

0.231

Gnomad NFE

AF:

0.331

Gnomad OTH

AF:

0.253

GnomAD4 exome

AF:

0.293

AC:

130820

AN:

447156

Hom.:

20677

Cov.:

AF XY:

0.295

AC XY:

72296

AN XY:

244816

show subpopulations

African (AFR)

AF:

0.197

AC:

2640

AN:

13398

American (AMR)

AF:

0.150

AC:

4668

AN:

31170

Ashkenazi Jewish (ASJ)

AF:

0.261

AC:

4362

AN:

16688

East Asian (EAS)

AF:

0.110

AC:

2428

AN:

22086

South Asian (SAS)

AF:

0.295

AC:

17946

AN:

60860

European-Finnish (FIN)

AF:

0.389

AC:

8653

AN:

22232

Middle Eastern (MID)

AF:

0.221

AC:

789

AN:

3576

European-Non Finnish (NFE)

AF:

0.327

AC:

82730

AN:

253074

Other (OTH)

AF:

0.274

AC:

6604

AN:

24072

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.509

Heterozygous variant carriers

5085

10170

15254

20339

25424

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

406

812

1218

1624

2030

<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:

0.273

AC:

41501

AN:

152044

Hom.:

6190

Cov.:

AF XY:

0.272

AC XY:

20179

AN XY:

74294

show subpopulations

African (AFR)

AF:

0.203

AC:

8408

AN:

41476

American (AMR)

AF:

0.178

AC:

2722

AN:

15296

Ashkenazi Jewish (ASJ)

AF:

0.262

AC:

907

AN:

3468

East Asian (EAS)

AF:

0.140

AC:

727

AN:

5180

South Asian (SAS)

AF:

0.293

AC:

1411

AN:

4814

European-Finnish (FIN)

AF:

0.370

AC:

3896

AN:

10542

Middle Eastern (MID)

AF:

0.241

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.331

AC:

22513

AN:

67952

Other (OTH)

AF:

0.253

AC:

534

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.505

Heterozygous variant carriers

1535

3071

4606

6142

7677

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

428

856

1284

1712

2140

<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:

0.288

Hom.:

9690

Bravo

AF:

0.247

Asia WGS

AF:

0.221

AC:

769

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.89

CADD

Benign

4.4

(source)

DANN

Benign

0.75

PhyloP100

0.14

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

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

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over