Genetic Variant KRT14:c.1274+35dupC (chr17-41583199-T-TG) – ACMG Classification: Benign (-10 pts)

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

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 links:

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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 id 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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
KRT14	NM_000526.5 link	c.1274+35dupC		intron_variant	Intron 6 of 7	ENST00000167586.7	NP_000517.3	P02533

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein	UniProt
KRT14	ENST00000167586.7 link	c.1274+35_1274+36insC	intron_variant	Intron 6 of 7	1	NM_000526.5	ENSP00000167586.6	P02533
KRT14	ENST00000441550.2 link	n.221+35_221+36insC	intron_variant	Intron 1 of 1	2
KRT14	ENST00000476662.1 link	n.49_50insC	downstream_gene_variant		2

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

Gnomad4 AFR exome

AF:

0.136

AC:

4403

AN:

32418

Gnomad4 AMR exome

AF:

0.00777

AC:

346

AN:

44502

Gnomad4 ASJ exome

AF:

0.00641

AC:

165

AN:

25740

Gnomad4 EAS exome

AF:

0.000409

AC:

AN:

39166

Gnomad4 SAS exome

AF:

0.000680

AC:

AN:

85282

Gnomad4 FIN exome

AF:

0.000916

AC:

AN:

51314

Gnomad4 NFE exome

AF:

0.000705

AC:

750

AN:

1063776

Gnomad4 Remaining exome

AF:

0.0109

AC:

637

AN:

58426

Heterozygous variant carriers

341

683

1024

1366

1707

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

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

Gnomad4 AFR

AF:

0.129

AC:

0.128659

AN:

0.128659

Gnomad4 AMR

AF:

0.0159

AC:

0.0159054

AN:

0.0159054

Gnomad4 ASJ

AF:

0.00678

AC:

0.00678066

AN:

0.00678066

Gnomad4 EAS

AF:

0.000606

AC:

0.000606061

AN:

0.000606061

Gnomad4 SAS

AF:

0.000871

AC:

0.000870701

AN:

0.000870701

Gnomad4 FIN

AF:

0.00

AC:

AN:

Gnomad4 NFE

AF:

0.00107

AC:

0.00106944

AN:

0.00106944

Gnomad4 OTH

AF:

0.0211

AC:

0.0211406

AN:

0.0211406

Heterozygous variant carriers

208

416

623

831

1039

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

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

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Mar 03, 2015

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

Mutation Taster

=100/0

polymorphism (auto)

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