Variant 17-41619618-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BS1BS2

The ENST00000311208.13(KRT17):c.1275G>A(p.Glu425=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0273 in 1,612,184 control chromosomes in the GnomAD database, including 710 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.021 ( 54 hom., cov: 32)

Exomes 𝑓: 0.028 ( 656 hom. )

Consequence

KRT17
ENST00000311208.13 synonymous

Scores

Clinical Significance

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

Conservation

PhyloP100: 1.13

Variant links:

Genes affected

KRT17 (HGNC:6427): (keratin 17) This gene encodes the type I intermediate filament chain keratin 17, expressed in nail bed, hair follicle, sebaceous glands, and other epidermal appendages. Mutations in this gene lead to Jackson-Lawler type pachyonychia congenita and steatocystoma multiplex. [provided by RefSeq, Aug 2008]

KRT17 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.5).

BP6

Variant 17-41619618-C-T is Benign according to our data. Variant chr17-41619618-C-T is described in ClinVar as [Benign]. Clinvar id is 1599894.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=1.13 with no splicing effect.

BS1

Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.0212 (3236/152288) while in subpopulation NFE AF= 0.0305 (2071/68000). AF 95% confidence interval is 0.0294. There are 54 homozygotes in gnomad4. There are 1536 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High AC in GnomAd4 at 3236 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
KRT17	NM_000422.3 linkuse as main transcript	c.1275G>A	p.Glu425=	synonymous_variant	8/8	ENST00000311208.13	NP_000413.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris
KRT17	ENST00000311208.13 linkuse as main transcript	c.1275G>A	p.Glu425=	synonymous_variant	8/8	1	NM_000422.3	ENSP00000308452	P1
KRT17	ENST00000493253.5 linkuse as main transcript	n.1662G>A		non_coding_transcript_exon_variant	7/7	2
KRT17	ENST00000649249.1 linkuse as main transcript	n.551G>A		non_coding_transcript_exon_variant	4/4

Frequencies

GnomAD3 genomes

AF:

0.0213

AC:

3237

AN:

152170

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00654

Gnomad AMI

AF:

0.0385

Gnomad AMR

AF:

0.0281

Gnomad ASJ

AF:

0.0308

Gnomad EAS

AF:

0.000385

Gnomad SAS

AF:

0.00621

Gnomad FIN

AF:

0.0202

Gnomad MID

AF:

0.0253

Gnomad NFE

AF:

0.0305

Gnomad OTH

AF:

0.0330

GnomAD3 exomes

AF:

0.0216

AC:

5424

AN:

251130

Hom.:

AF XY:

0.0214

AC XY:

2906

AN XY:

135746

show subpopulations

Gnomad AFR exome

AF:

0.00480

Gnomad AMR exome

AF:

0.0215

Gnomad ASJ exome

AF:

0.0296

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00552

Gnomad FIN exome

AF:

0.0209

Gnomad NFE exome

AF:

0.0307

Gnomad OTH exome

AF:

0.0326

GnomAD4 exome

AF:

0.0279

AC:

40796

AN:

1459896

Hom.:

656

Cov.:

AF XY:

0.0273

AC XY:

19833

AN XY:

726246

show subpopulations

Gnomad4 AFR exome

AF:

0.00464

Gnomad4 AMR exome

AF:

0.0225

Gnomad4 ASJ exome

AF:

0.0292

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00602

Gnomad4 FIN exome

AF:

0.0214

Gnomad4 NFE exome

AF:

0.0319

Gnomad4 OTH exome

AF:

0.0278

GnomAD4 genome

AF:

0.0212

AC:

3236

AN:

152288

Hom.:

Cov.:

AF XY:

0.0206

AC XY:

1536

AN XY:

74472

show subpopulations

Gnomad4 AFR

AF:

0.00652

Gnomad4 AMR

AF:

0.0280

Gnomad4 ASJ

AF:

0.0308

Gnomad4 EAS

AF:

0.000386

Gnomad4 SAS

AF:

0.00621

Gnomad4 FIN

AF:

0.0202

Gnomad4 NFE

AF:

0.0305

Gnomad4 OTH

AF:

0.0327

Alfa

AF:

0.0276

Hom.:

Bravo

AF:

0.0214

Asia WGS

AF:

0.00289

AC:

AN:

3478

EpiCase

AF:

0.0320

EpiControl

AF:

0.0339

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 29, 2024	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.50

CADD

Benign

DANN

Benign

0.59

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.14

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