Variant 17-41620565-G-GA details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_ModerateBS1BS2

The NM_000422.3(KRT17):c.1182-8_1182-7insT variant causes a splice region, splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0147 in 145,326 control chromosomes in the GnomAD database, including 28 homozygotes. 1/1 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.015 ( 28 hom., cov: 31)

Exomes 𝑓: 0.085 ( 45 hom. )

Failed GnomAD Quality Control

Consequence

KRT17
NM_000422.3 splice_region, splice_polypyrimidine_tract, intron

Scores

Not classified

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.262

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:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -10 ACMG points.

BP6

Variant 17-41620565-G-GA is Benign according to our data. Variant chr17-41620565-G-GA is described in ClinVar as [Benign]. Clinvar id is 1528628.Status of the report is criteria_provided_single_submitter, 1 stars.

BS1

Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.0147 (2140/145326) while in subpopulation NFE AF= 0.0195 (1281/65662). AF 95% confidence interval is 0.0186. There are 28 homozygotes in gnomad4. There are 961 alleles in male gnomad4 subpopulation. Median coverage is 31. This position pass quality control queck.

BS2

High AC in GnomAd4 at 2140 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
KRT17	NM_000422.3 linkuse as main transcript	c.1182-8_1182-7insT		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		ENST00000311208.13	NP_000413.1

Ensembl

Gene	Transcript	HGVSc	Effect	TSL	MANE	Protein	Appris
KRT17	ENST00000311208.13 linkuse as main transcript	c.1182-8_1182-7insT	splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant	1	NM_000422.3	ENSP00000308452	P1
KRT17	ENST00000648859.1 linkuse as main transcript	c.172-8_172-7insT	splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant			ENSP00000497161
KRT17	ENST00000493253.5 linkuse as main transcript	n.1569-8_1569-7insT	splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant, non_coding_transcript_variant	2
KRT17	ENST00000649249.1 linkuse as main transcript	n.458-8_458-7insT	splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes

AF:

0.0147

AC:

2139

AN:

145248

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00618

Gnomad AMI

AF:

0.0391

Gnomad AMR

AF:

0.0176

Gnomad ASJ

AF:

0.0533

Gnomad EAS

AF:

0.00120

Gnomad SAS

AF:

0.00612

Gnomad FIN

AF:

0.00559

Gnomad MID

AF:

0.0367

Gnomad NFE

AF:

0.0195

Gnomad OTH

AF:

0.0218

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR;InbreedingCoeff

AF:

0.0852

AC:

62484

AN:

732962

Hom.:

Cov.:

AF XY:

0.0839

AC XY:

30025

AN XY:

357924

show subpopulations

Gnomad4 AFR exome

AF:

0.0439

Gnomad4 AMR exome

AF:

0.0633

Gnomad4 ASJ exome

AF:

0.132

Gnomad4 EAS exome

AF:

0.0366

Gnomad4 SAS exome

AF:

0.0540

Gnomad4 FIN exome

AF:

0.0349

Gnomad4 NFE exome

AF:

0.0918

Gnomad4 OTH exome

AF:

0.0861

GnomAD4 genome

AF:

0.0147

AC:

2140

AN:

145326

Hom.:

Cov.:

AF XY:

0.0136

AC XY:

961

AN XY:

70470

show subpopulations

Gnomad4 AFR

AF:

0.00616

Gnomad4 AMR

AF:

0.0176

Gnomad4 ASJ

AF:

0.0533

Gnomad4 EAS

AF:

0.00120

Gnomad4 SAS

AF:

0.00657

Gnomad4 FIN

AF:

0.00559

Gnomad4 NFE

AF:

0.0195

Gnomad4 OTH

AF:

0.0217

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Jan 20, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

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