12-52251970-T-C

Position:

• chr12-52251970-T-C

Variant summary

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

The NR_146088.1(KRT87P):​n.1243+57A>G variant causes a intron, non coding transcript 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: KRT87P NR_146088.1 intron, non_coding_transcript
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.140

Genes affected

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

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]

ACMG classification

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
KRT87P	NR_146088.1	n.1243+57A>G		intron_variant, non_coding_transcript_variant
KRT7	XM_011538325.3	c.*61T>C		3_prime_UTR_variant	8/8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
KRT87P	ENST00000529785.1	n.1602+57A>G		intron_variant, non_coding_transcript_variant		2
KRT87P	ENST00000534226.5	n.1288+57A>G		intron_variant, non_coding_transcript_variant
KRT86	ENST00000553310.6	c.-5+2542T>C		intron_variant		4
KRT7	ENST00000548657.5	n.423T>C		non_coding_transcript_exon_variant	3/3	3

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

Gnomad4 AFR exome AF: 0.197

Gnomad4 AMR exome AF: 0.150

Gnomad4 ASJ exome AF: 0.261

Gnomad4 EAS exome AF: 0.110

Gnomad4 SAS exome AF: 0.295

Gnomad4 FIN exome AF: 0.389

Gnomad4 NFE exome AF: 0.327

Gnomad4 OTH exome AF: 0.274

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

Gnomad4 AFR AF: 0.203

Gnomad4 AMR AF: 0.178

Gnomad4 ASJ AF: 0.262

Gnomad4 EAS AF: 0.140

Gnomad4 SAS AF: 0.293

Gnomad4 FIN AF: 0.370

Gnomad4 NFE AF: 0.331

Gnomad4 OTH AF: 0.253

Alfa AF: 0.296 Hom.: 6941

Bravo AF: 0.247

Asia WGS AF: 0.221 AC: 769 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	4.4
DANN	Benign	0.75

Splicing

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

Publications

LitVar

Other links and lift over

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