chr12-52382151-T-G

Position:

• chr12-52382151-T-G

Variant summary

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

The NM_033045.4(KRT84):​c.912+286A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.324 in 152,066 control chromosomes in the GnomAD database, including 10,141 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 0.32 (10141 hom., cov: 33)
• Consequence: KRT84 NM_033045.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.121

Genes affected

KRT84 (HGNC:6461): (keratin 84) The protein encoded by this gene is a member of the keratin gene family. As a type II hair keratin, it is a basic protein which heterodimerizes with type I keratins to form hair and nails. The type II hair keratins are clustered in a region of chromosome 12q13 and are grouped into two distinct subfamilies based on structure similarity. One subfamily, consisting of KRTHB1, KRTHB3, and KRTHB6, is highly related. The other less-related subfamily includes KRTHB2, KRTHB4, and KRTHB5. All hair keratins are expressed in the hair follicle; this hair keratin is contained primarily in the filiform tongue papilla, among other hair keratins. [provided by RefSeq, Jul 2008]

ENSG00000258253 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.577 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
KRT84	NM_033045.4	c.912+286A>C		intron_variant		ENST00000257951.3	NP_149034.2
KRT84	XM_011538335.3	c.912+286A>C		intron_variant			XP_011536637.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
KRT84	ENST00000257951.3	c.912+286A>C		intron_variant		1	NM_033045.4	ENSP00000257951.3
ENSG00000258253	ENST00000547174.1	n.146+1546T>G		intron_variant		4

Frequencies

GnomAD3 genomes AF: 0.324 AC: 49238 AN: 151948 Hom.: 10131 Cov.: 33

Gnomad AFR AF: 0.583

Gnomad AMI AF: 0.229

Gnomad AMR AF: 0.330

Gnomad ASJ AF: 0.177

Gnomad EAS AF: 0.174

Gnomad SAS AF: 0.223

Gnomad FIN AF: 0.231

Gnomad MID AF: 0.187

Gnomad NFE AF: 0.208

Gnomad OTH AF: 0.301

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

GnomAD4 genome AF: 0.324 AC: 49291 AN: 152066 Hom.: 10141 Cov.: 33 AF XY: 0.324 AC XY: 24086 AN XY: 74346

Gnomad4 AFR AF: 0.583

Gnomad4 AMR AF: 0.330

Gnomad4 ASJ AF: 0.177

Gnomad4 EAS AF: 0.174

Gnomad4 SAS AF: 0.222

Gnomad4 FIN AF: 0.231

Gnomad4 NFE AF: 0.208

Gnomad4 OTH AF: 0.299

Alfa AF: 0.290 Hom.: 1263

Bravo AF: 0.341

Asia WGS AF: 0.227 AC: 790 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	5.6
DANN	Benign	0.49

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: rs1613631; hg19: chr12-52775935;