chr12-52298174-T-C

Position:

• chr12-52298174-T-C

Variant summary

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

The NM_001320198.2(KRT86):​c.-4-3739T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.128 in 152,220 control chromosomes in the GnomAD database, including 1,321 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 0.13 (1321 hom., cov: 33)
• Consequence: KRT86 NM_001320198.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.184

Genes affected

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]

KRT81 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.73).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.166 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
KRT86	NM_001320198.2	c.-4-3739T>C		intron_variant		ENST00000423955.7	NP_001307127.1
KRT81	XM_047428838.1	c.-6709A>G		5_prime_UTR_variant	2/10		XP_047284794.1
KRT86	XM_005268866.5	c.130-3641T>C		intron_variant			XP_005268923.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
KRT86	ENST00000423955.7	c.-4-3739T>C		intron_variant		2	NM_001320198.2	ENSP00000444533	P1
KRT86	ENST00000553310.6	c.-4-3739T>C		intron_variant		4		ENSP00000452237

Frequencies

GnomAD3 genomes AF: 0.128 AC: 19500 AN: 152102 Hom.: 1321 Cov.: 33

Gnomad AFR AF: 0.169

Gnomad AMI AF: 0.174

Gnomad AMR AF: 0.0802

Gnomad ASJ AF: 0.0668

Gnomad EAS AF: 0.122

Gnomad SAS AF: 0.0958

Gnomad FIN AF: 0.154

Gnomad MID AF: 0.0287

Gnomad NFE AF: 0.116

Gnomad OTH AF: 0.116

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

GnomAD4 genome AF: 0.128 AC: 19519 AN: 152220 Hom.: 1321 Cov.: 33 AF XY: 0.128 AC XY: 9555 AN XY: 74432

Gnomad4 AFR AF: 0.169

Gnomad4 AMR AF: 0.0802

Gnomad4 ASJ AF: 0.0668

Gnomad4 EAS AF: 0.123

Gnomad4 SAS AF: 0.0959

Gnomad4 FIN AF: 0.154

Gnomad4 NFE AF: 0.116

Gnomad4 OTH AF: 0.116

Alfa AF: 0.108 Hom.: 1035

Bravo AF: 0.123

Asia WGS AF: 0.0990 AC: 345 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.73
CADD	Benign	2.6
DANN	Benign	0.83

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: rs17655565; hg19: chr12-52691958;