17-41583199-TG-TGG

Variant names:

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP6_ModerateBA1

The NM_000526.5(KRT14):c.1274+35dupC variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0077 in 1,552,426 control chromosomes in the GnomAD database, including 580 homozygotes. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.037 ( 303 hom., cov: 31)

Exomes 𝑓: 0.0046 ( 277 hom. )

Consequence

KRT14
NM_000526.5 intron

Scores

Not classified

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.217

Publications

1 publications found

Variant links:

Genes affected

KRT14 (HGNC:6416): (keratin 14) This gene encodes a member of the keratin family, the most diverse group of intermediate filaments. This gene product, a type I keratin, is usually found as a heterotetramer with two keratin 5 molecules, a type II keratin. Together they form the cytoskeleton of epithelial cells. Mutations in the genes for these keratins are associated with epidermolysis bullosa simplex. At least one pseudogene has been identified at 17p12-p11. [provided by RefSeq, Jul 2008]

KRT14 Gene-Disease associations (from GenCC):

epidermolysis bullosa simplex 1A, generalized severe
Inheritance: AD Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Genomics England PanelApp, Ambry Genetics, Orphanet
Naegeli-Franceschetti-Jadassohn syndrome
Inheritance: AD Classification: DEFINITIVE, STRONG, SUPPORTIVE, LIMITED Submitted by: Labcorp Genetics (formerly Invitae), G2P, Ambry Genetics, Orphanet, Genomics England PanelApp
epidermolysis bullosa simplex
Inheritance: AR Classification: DEFINITIVE Submitted by: G2P
epidermolysis bullosa simplex 1D, generalized, intermediate or severe, autosomal recessive
Inheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics, Genomics England PanelApp, Orphanet
dermatopathia pigmentosa reticularis
Inheritance: AD Classification: STRONG, SUPPORTIVE Submitted by: Genomics England PanelApp, Orphanet
epidermolysis bullosa simplex 1B, generalized intermediate
Inheritance: AD Classification: STRONG, SUPPORTIVE Submitted by: Genomics England PanelApp, Orphanet, Labcorp Genetics (formerly Invitae)
epidermolysis bullosa simplex 1C, localized
Inheritance: AD Classification: STRONG, SUPPORTIVE Submitted by: Orphanet, Genomics England PanelApp
epidermolysis bullosa simplex 2F, with mottled pigmentation
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

KRT14 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -10 ACMG points.

BP6

Variant 17-41583199-T-TG is Benign according to our data. Variant chr17-41583199-T-TG is described in ClinVar as Benign. ClinVar VariationId is 1221511.Status of the report is criteria_provided_single_submitter, 1 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.126 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000526.5. 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
	KRT14	NM_000526.5	MANE Select	c.1274+35dupC		intron	N/A	NP_000517.3

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
KRT14	ENST00000167586.7	TSL:1 MANE Select	c.1274+35_1274+36insC	intron	N/A	ENSP00000167586.6	P02533
KRT14	ENST00000441550.2	TSL:2	n.221+35_221+36insC	intron	N/A
KRT14	ENST00000476662.1	TSL:2	n.49_50insC	downstream_gene	N/A

Frequencies

GnomAD3 genomes

AF:

0.0371

AC:

5441

AN:

146498

Hom.:

303

Cov.:

show subpopulations

Gnomad AFR

AF:

0.128

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0159

Gnomad ASJ

AF:

0.00678

Gnomad EAS

AF:

0.000605

Gnomad SAS

AF:

0.00109

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.0192

Gnomad NFE

AF:

0.00107

Gnomad OTH

AF:

0.0214

GnomAD2 exomes

AF:

0.0102

AC:

2539

AN:

247756

AF XY:

0.00771

show subpopulations

Gnomad AFR exome

AF:

0.130

Gnomad AMR exome

AF:

0.00696

Gnomad ASJ exome

AF:

0.00735

Gnomad EAS exome

AF:

0.0000547

Gnomad FIN exome

AF:

0.0000464

Gnomad NFE exome

AF:

0.00113

Gnomad OTH exome

AF:

0.00713

GnomAD4 exome

AF:

0.00462

AC:

6488

AN:

1405816

Hom.:

277

Cov.:

AF XY:

0.00398

AC XY:

2791

AN XY:

701802

show subpopulations

African (AFR)

AF:

0.136

AC:

4403

AN:

32418

American (AMR)

AF:

0.00777

AC:

346

AN:

44502

Ashkenazi Jewish (ASJ)

AF:

0.00641

AC:

165

AN:

25740

East Asian (EAS)

AF:

0.000409

AC:

AN:

39166

South Asian (SAS)

AF:

0.000680

AC:

AN:

85282

European-Finnish (FIN)

AF:

0.000916

AC:

AN:

51314

Middle Eastern (MID)

AF:

0.0127

AC:

AN:

5192

European-Non Finnish (NFE)

AF:

0.000705

AC:

750

AN:

1063776

Other (OTH)

AF:

0.0109

AC:

637

AN:

58426

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.434

Heterozygous variant carriers

341

683

1024

1366

1707

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

154

308

462

616

770

<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:

0.0373

AC:

5465

AN:

146610

Hom.:

303

Cov.:

AF XY:

0.0367

AC XY:

2625

AN XY:

71512

show subpopulations

African (AFR)

AF:

0.129

AC:

5081

AN:

39492

American (AMR)

AF:

0.0159

AC:

234

AN:

14712

Ashkenazi Jewish (ASJ)

AF:

0.00678

AC:

AN:

3392

East Asian (EAS)

AF:

0.000606

AC:

AN:

4950

South Asian (SAS)

AF:

0.000871

AC:

AN:

4594

European-Finnish (FIN)

AF:

0.00

AC:

AN:

9866

Middle Eastern (MID)

AF:

0.0208

AC:

AN:

288

European-Non Finnish (NFE)

AF:

0.00107

AC:

AN:

66390

Other (OTH)

AF:

0.0211

AC:

AN:

2034

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.470

Heterozygous variant carriers

208

416

623

831

1039

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

108

162

216

270

<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:

0.00431

Hom.:

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

PhyloP100

-0.22

Mutation Taster

=100/0

polymorphism (auto)

(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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

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