chr12-52676904-G-A

Position:

• chr12-52676904-G-A

Variant summary

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

The NM_006121.4(KRT1):​c.1254+155C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.342 in 152,050 control chromosomes in the GnomAD database, including 9,072 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 0.34 (9072 hom., cov: 33)
• Consequence: KRT1 NM_006121.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.61

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]

KRT1 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.57 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
KRT1	NM_006121.4	c.1254+155C>T		intron_variant		ENST00000252244.3	NP_006112.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
KRT1	ENST00000252244.3	c.1254+155C>T		intron_variant		1	NM_006121.4	ENSP00000252244.3
KRT1	ENST00000548765.1	n.328+155C>T		intron_variant		2

Frequencies

GnomAD3 genomes AF: 0.342 AC: 52014 AN: 151932 Hom.: 9072 Cov.: 33

Gnomad AFR AF: 0.310

Gnomad AMI AF: 0.140

Gnomad AMR AF: 0.295

Gnomad ASJ AF: 0.339

Gnomad EAS AF: 0.586

Gnomad SAS AF: 0.348

Gnomad FIN AF: 0.389

Gnomad MID AF: 0.285

Gnomad NFE AF: 0.349

Gnomad OTH AF: 0.349

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

GnomAD4 genome AF: 0.342 AC: 52018 AN: 152050 Hom.: 9072 Cov.: 33 AF XY: 0.344 AC XY: 25590 AN XY: 74322

Gnomad4 AFR AF: 0.310

Gnomad4 AMR AF: 0.294

Gnomad4 ASJ AF: 0.339

Gnomad4 EAS AF: 0.587

Gnomad4 SAS AF: 0.348

Gnomad4 FIN AF: 0.389

Gnomad4 NFE AF: 0.349

Gnomad4 OTH AF: 0.345

Alfa AF: 0.344 Hom.: 18921

Bravo AF: 0.336

Asia WGS AF: 0.405 AC: 1411 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.12
DANN	Benign	0.41

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: rs597685; hg19: chr12-53070688;