rs2741159

chr12-52677598-A-Cchr12-52677598-A-T

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_006121.4(KRT1):c.963+52T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.383 in 1,603,488 control chromosomes in the GnomAD database, including 122,818 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.38 (11317 hom., cov: 32)
  • Exomes 𝑓: 0.38 (111501 hom.)
• Consequence: KRT1 NM_006121.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1 O:1
• Conservation: PhyloP100: -1.67

Genes affected

KRT1 (HGNC:6412): (keratin 1) The protein encoded by this gene is a member of the keratin gene family. The type II cytokeratins consist of basic or neutral proteins which are arranged in pairs of heterotypic keratin chains coexpressed during differentiation of simple and stratified epithelial tissues. This type II cytokeratin is specifically expressed in the spinous and granular layers of the epidermis with family member KRT10 and mutations in these genes have been associated with bullous congenital ichthyosiform erythroderma. The type II cytokeratins are clustered in a region of chromosome 12q12-q13. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BP6: Variant 12-52677598-A-C is Benign according to our data. Variant chr12-52677598-A-C is described in ClinVar as [Benign]. Clinvar id is 66667.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.406 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
KRT1	NM_006121.4	c.963+52T>G		intron_variant		ENST00000252244.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
KRT1	ENST00000252244.3	c.963+52T>G		intron_variant		1	NM_006121.4	P1

Frequencies

GnomAD3 genomes AF: 0.376 AC: 57099 AN: 151982 Hom.: 11297 Cov.: 32

Gnomad AFR AF: 0.365

Gnomad AMI AF: 0.644

Gnomad AMR AF: 0.373

Gnomad ASJ AF: 0.383

Gnomad EAS AF: 0.0202

Gnomad SAS AF: 0.260

Gnomad FIN AF: 0.408

Gnomad MID AF: 0.316

Gnomad NFE AF: 0.410

Gnomad OTH AF: 0.362

GnomAD4 exome AF: 0.384 AC: 557323 AN: 1451388 Hom.: 111501 Cov.: 31 AF XY: 0.380 AC XY: 274823 AN XY: 722718

Gnomad4 AFR exome AF: 0.366

Gnomad4 AMR exome AF: 0.347

Gnomad4 ASJ exome AF: 0.385

Gnomad4 EAS exome AF: 0.0125

Gnomad4 SAS exome AF: 0.256

Gnomad4 FIN exome AF: 0.412

Gnomad4 NFE exome AF: 0.409

Gnomad4 OTH exome AF: 0.364

GnomAD4 genome AF: 0.376 AC: 57151 AN: 152100 Hom.: 11317 Cov.: 32 AF XY: 0.369 AC XY: 27422 AN XY: 74352

Gnomad4 AFR AF: 0.365

Gnomad4 AMR AF: 0.373

Gnomad4 ASJ AF: 0.383

Gnomad4 EAS AF: 0.0202

Gnomad4 SAS AF: 0.259

Gnomad4 FIN AF: 0.408

Gnomad4 NFE AF: 0.410

Gnomad4 OTH AF: 0.370

Alfa AF: 0.358 Hom.: 2834

Bravo AF: 0.374

Asia WGS AF: 0.233 AC: 809 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1 Other:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1 Other:1

Benign, criteria provided, single submitter	clinical testing	GeneDx	Mar 03, 2015	- -
not provided, no classification provided	literature only	Epithelial Biology; Institute of Medical Biology, Singapore	-	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
Cadd	Benign	0.19
Dann	Benign	0.60

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: rs2741159; hg19: chr12-53071382;