rs2189387

Positions:

• chr17-40883854-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_019010.3(KRT20):​c.390+942G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.224 in 152,194 control chromosomes in the GnomAD database, including 4,598 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.22 (4598 hom., cov: 32)
• Consequence: KRT20 NM_019010.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.567

Genes affected

KRT20 (HGNC:20412): (keratin 20) The protein encoded by this gene is a member of the keratin family. The keratins are intermediate filament proteins responsible for the structural integrity of epithelial cells and are subdivided into cytokeratins and hair keratins. The type I cytokeratins consist of acidic proteins which are arranged in pairs of heterotypic keratin chains. This cytokeratin is a major cellular protein of mature enterocytes and goblet cells and is specifically expressed in the gastric and intestinal mucosa. The type I cytokeratin genes are clustered in a region of chromosome 17q12-q21. [provided by RefSeq, Jul 2008]

LOC105371777 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.319 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
KRT20	NM_019010.3	c.390+942G>A		intron_variant		ENST00000167588.4
LOC105371777	XR_934754.3	n.63+32994C>T		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
KRT20	ENST00000167588.4	c.390+942G>A		intron_variant		1	NM_019010.3	P1
KRT20	ENST00000482529.1	n.115+942G>A		intron_variant, non_coding_transcript_variant		2

Frequencies

GnomAD3 genomes AF: 0.224 AC: 34078 AN: 152076 Hom.: 4602 Cov.: 32

Gnomad AFR AF: 0.0629

Gnomad AMI AF: 0.410

Gnomad AMR AF: 0.227

Gnomad ASJ AF: 0.356

Gnomad EAS AF: 0.331

Gnomad SAS AF: 0.251

Gnomad FIN AF: 0.259

Gnomad MID AF: 0.231

Gnomad NFE AF: 0.296

Gnomad OTH AF: 0.238

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.224 AC: 34066 AN: 152194 Hom.: 4598 Cov.: 32 AF XY: 0.224 AC XY: 16674 AN XY: 74410

Gnomad4 AFR AF: 0.0627

Gnomad4 AMR AF: 0.226

Gnomad4 ASJ AF: 0.356

Gnomad4 EAS AF: 0.332

Gnomad4 SAS AF: 0.251

Gnomad4 FIN AF: 0.259

Gnomad4 NFE AF: 0.296

Gnomad4 OTH AF: 0.236

Alfa AF: 0.266 Hom.: 2870

Bravo AF: 0.215

Asia WGS AF: 0.257 AC: 894 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.92
DANN	Benign	0.61

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: rs2189387; hg19: chr17-39040106;