17-41567795-T-C

Position:

• chr17-41567795-T-C

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_000226.4(KRT9):​c.1395-45A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.581 in 1,612,090 control chromosomes in the GnomAD database, including 279,031 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.57 (25232 hom., cov: 32)
  • Exomes 𝑓: 0.58 (253799 hom.)
• Consequence: KRT9 NM_000226.4 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.692

Genes affected

KRT9 (HGNC:6447): (keratin 9) This gene encodes the type I keratin 9, an intermediate filament chain expressed only in the terminally differentiated epidermis of palms and soles. Mutations in this gene cause epidermolytic palmoplantar keratoderma. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BP6: Variant 17-41567795-T-C is Benign according to our data. Variant chr17-41567795-T-C is described in ClinVar as [Benign]. Clinvar id is 1283937.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.926 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
KRT9	NM_000226.4	c.1395-45A>G		intron_variant		ENST00000246662.9	NP_000217.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
KRT9	ENST00000246662.9	c.1395-45A>G		intron_variant		1	NM_000226.4	ENSP00000246662.4
KRT9	ENST00000588431.1	c.696-45A>G		intron_variant		1		ENSP00000467932.1

Frequencies

GnomAD3 genomes AF: 0.566 AC: 85982 AN: 152008 Hom.: 25217 Cov.: 32

Gnomad AFR AF: 0.453

Gnomad AMI AF: 0.769

Gnomad AMR AF: 0.665

Gnomad ASJ AF: 0.589

Gnomad EAS AF: 0.948

Gnomad SAS AF: 0.721

Gnomad FIN AF: 0.653

Gnomad MID AF: 0.430

Gnomad NFE AF: 0.555

Gnomad OTH AF: 0.549

GnomAD3 exomes AF: 0.640 AC: 157397 AN: 245974 Hom.: 52412 AF XY: 0.636 AC XY: 85080 AN XY: 133738

Gnomad AFR exome AF: 0.455

Gnomad AMR exome AF: 0.775

Gnomad ASJ exome AF: 0.586

Gnomad EAS exome AF: 0.942

Gnomad SAS exome AF: 0.700

Gnomad FIN exome AF: 0.663

Gnomad NFE exome AF: 0.560

Gnomad OTH exome AF: 0.598

GnomAD4 exome AF: 0.583 AC: 851100 AN: 1459962 Hom.: 253799 Cov.: 59 AF XY: 0.586 AC XY: 425512 AN XY: 726434

Gnomad4 AFR exome AF: 0.449

Gnomad4 AMR exome AF: 0.760

Gnomad4 ASJ exome AF: 0.588

Gnomad4 EAS exome AF: 0.957

Gnomad4 SAS exome AF: 0.697

Gnomad4 FIN exome AF: 0.657

Gnomad4 NFE exome AF: 0.555

Gnomad4 OTH exome AF: 0.582

GnomAD4 genome AF: 0.566 AC: 86042 AN: 152128 Hom.: 25232 Cov.: 32 AF XY: 0.575 AC XY: 42741 AN XY: 74362

Gnomad4 AFR AF: 0.453

Gnomad4 AMR AF: 0.665

Gnomad4 ASJ AF: 0.589

Gnomad4 EAS AF: 0.948

Gnomad4 SAS AF: 0.720

Gnomad4 FIN AF: 0.653

Gnomad4 NFE AF: 0.555

Gnomad4 OTH AF: 0.551

Alfa AF: 0.553 Hom.: 30196

Bravo AF: 0.563

Asia WGS AF: 0.805 AC: 2798 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Nov 12, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	1.2
DANN	Benign	0.33

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

Other links and lift over

dbSNP: rs1008753; hg19: chr17-39724047;