chr12-52361313-A-T

Position:

• chr12-52361313-A-T

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_002283.4(KRT85):​c.1330+154T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.565 in 152,108 control chromosomes in the GnomAD database, including 25,079 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency: Genomes: 𝑓 0.57 (25079 hom., cov: 33)
• Consequence: KRT85 NM_002283.4 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -1.71

Genes affected

KRT85 (HGNC:6462): (keratin 85) 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. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BP6: Variant 12-52361313-A-T is Benign according to our data. Variant chr12-52361313-A-T is described in ClinVar as [Benign]. Clinvar id is 1231043.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.709 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
KRT85	NM_002283.4	c.1330+154T>A		intron_variant		ENST00000257901.7	NP_002274.1
KRT85	NM_001300810.1	c.694+154T>A		intron_variant			NP_001287739.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
KRT85	ENST00000257901.7	c.1330+154T>A		intron_variant		1	NM_002283.4	ENSP00000257901	P1
KRT85	ENST00000544265.1	c.694+154T>A		intron_variant		2		ENSP00000440240

Frequencies

GnomAD3 genomes AF: 0.565 AC: 85888 AN: 151988 Hom.: 25044 Cov.: 33

Gnomad AFR AF: 0.716

Gnomad AMI AF: 0.520

Gnomad AMR AF: 0.506

Gnomad ASJ AF: 0.402

Gnomad EAS AF: 0.632

Gnomad SAS AF: 0.579

Gnomad FIN AF: 0.485

Gnomad MID AF: 0.487

Gnomad NFE AF: 0.503

Gnomad OTH AF: 0.533

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

GnomAD4 genome AF: 0.565 AC: 85986 AN: 152108 Hom.: 25079 Cov.: 33 AF XY: 0.564 AC XY: 41902 AN XY: 74342

Gnomad4 AFR AF: 0.716

Gnomad4 AMR AF: 0.505

Gnomad4 ASJ AF: 0.402

Gnomad4 EAS AF: 0.633

Gnomad4 SAS AF: 0.581

Gnomad4 FIN AF: 0.485

Gnomad4 NFE AF: 0.503

Gnomad4 OTH AF: 0.533

Alfa AF: 0.529 Hom.: 2743

Bravo AF: 0.574

Asia WGS AF: 0.602 AC: 2093 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Nov 12, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.068
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: rs1791627; hg19: chr12-52755097;