chr12-52251970-T-C

Variant names:

• chr12-52251970-T-C
• rs1894035
• ENST00000548657.5:n.423T>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000548657.5(KRT7):​n.423T>C variant causes a non coding transcript exon change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.288 in 599,200 control chromosomes in the GnomAD database, including 26,867 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 0.27 (6190 hom., cov: 33)
  • Exomes 𝑓: 0.29 (20677 hom.)
• Consequence: KRT7 ENST00000548657.5 non_coding_transcript_exon
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.140
• Publications: 8 publications found

Genes affected

KRT7 (HGNC:6445): (keratin 7) 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 simple epithelia lining the cavities of the internal organs and in the gland ducts and blood vessels. The genes encoding the type II cytokeratins are clustered in a region of chromosome 12q12-q13. Alternative splicing may result in several transcript variants; however, not all variants have been fully described. [provided by RefSeq, Jul 2008]

KRT86 (HGNC:6463): (keratin 86) This gene encodes a type II keratin protein, which heterodimerizes with type I keratins to form hair and nails. This gene is present in a cluster of related genes and pseudogenes on chromosome 12. Mutations in this gene have been observed in patients with the hair disease monilethrix. [provided by RefSeq, Feb 2016]

KRT87P (HGNC:):

KRT87P (HGNC:30198): (keratin 87, pseudogene) Located in extracellular space. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.328 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000548657.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KRT87P	NR_146088.1		n.1243+57A>G		intron	N/A

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KRT7	ENST00000548657.5	TSL:3	n.423T>C		non_coding_transcript_exon	Exon 3 of 3
	KRT86	ENST00000553310.6	TSL:4	c.-5+2542T>C		intron	N/A	ENSP00000452237.3
	KRT87P	ENST00000529785.1	TSL:2	n.1602+57A>G		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.273 AC: 41495 AN: 151924 Hom.: 6194 Cov.: 33

Gnomad AFR AF: 0.203

Gnomad AMI AF: 0.343

Gnomad AMR AF: 0.178

Gnomad ASJ AF: 0.262

Gnomad EAS AF: 0.140

Gnomad SAS AF: 0.293

Gnomad FIN AF: 0.370

Gnomad MID AF: 0.231

Gnomad NFE AF: 0.331

Gnomad OTH AF: 0.253

GnomAD4 exome AF: 0.293 AC: 130820 AN: 447156 Hom.: 20677 Cov.: 3 AF XY: 0.295 AC XY: 72296 AN XY: 244816

African (AFR) AF: 0.197 AC: 2640 AN: 13398

American (AMR) AF: 0.150 AC: 4668 AN: 31170

Ashkenazi Jewish (ASJ) AF: 0.261 AC: 4362 AN: 16688

East Asian (EAS) AF: 0.110 AC: 2428 AN: 22086

South Asian (SAS) AF: 0.295 AC: 17946 AN: 60860

European-Finnish (FIN) AF: 0.389 AC: 8653 AN: 22232

Middle Eastern (MID) AF: 0.221 AC: 789 AN: 3576

European-Non Finnish (NFE) AF: 0.327 AC: 82730 AN: 253074

Other (OTH) AF: 0.274 AC: 6604 AN: 24072

GnomAD4 genome AF: 0.273 AC: 41501 AN: 152044 Hom.: 6190 Cov.: 33 AF XY: 0.272 AC XY: 20179 AN XY: 74294

African (AFR) AF: 0.203 AC: 8408 AN: 41476

American (AMR) AF: 0.178 AC: 2722 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.262 AC: 907 AN: 3468

East Asian (EAS) AF: 0.140 AC: 727 AN: 5180

South Asian (SAS) AF: 0.293 AC: 1411 AN: 4814

European-Finnish (FIN) AF: 0.370 AC: 3896 AN: 10542

Middle Eastern (MID) AF: 0.241 AC: 71 AN: 294

European-Non Finnish (NFE) AF: 0.331 AC: 22513 AN: 67952

Other (OTH) AF: 0.253 AC: 534 AN: 2112

Alfa AF: 0.288 Hom.: 9690

Bravo AF: 0.247

Asia WGS AF: 0.221 AC: 769 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	4.4
DANN	Benign	0.75
PhyloP100		0.14
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs1894035; hg19: chr12-52645754; COSMIC: COSV57766439;