Variant chr12-52361557-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The ENST00000257901.7(KRT85):c.1299-59A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.194 in 1,522,212 control chromosomes in the GnomAD database, including 32,393 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.16 ( 2668 hom., cov: 33)

Exomes 𝑓: 0.20 ( 29725 hom. )

Consequence

KRT85
ENST00000257901.7 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -0.0360

Variant links:

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]

KRT85 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.81).

BP6

Variant 12-52361557-T-C is Benign according to our data. Variant chr12-52361557-T-C is described in ClinVar as [Benign]. Clinvar id is 1230825.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.484 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
KRT85	NM_002283.4 linkuse as main transcript	c.1299-59A>G		intron_variant		ENST00000257901.7	NP_002274.1
KRT85	NM_001300810.1 linkuse as main transcript	c.663-59A>G		intron_variant			NP_001287739.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
KRT85	ENST00000257901.7 linkuse as main transcript	c.1299-59A>G		intron_variant		1	NM_002283.4	ENSP00000257901	P1
KRT85	ENST00000544265.1 linkuse as main transcript	c.663-59A>G		intron_variant		2		ENSP00000440240

Frequencies

GnomAD3 genomes

AF:

0.162

AC:

24690

AN:

152094

Hom.:

2664

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0492

Gnomad AMI

AF:

0.0670

Gnomad AMR

AF:

0.200

Gnomad ASJ

AF:

0.225

Gnomad EAS

AF:

0.499

Gnomad SAS

AF:

0.185

Gnomad FIN

AF:

0.202

Gnomad MID

AF:

0.174

Gnomad NFE

AF:

0.187

Gnomad OTH

AF:

0.166

GnomAD4 exome

AF:

0.198

AC:

270618

AN:

1370000

Hom.:

29725

AF XY:

0.197

AC XY:

135494

AN XY:

686876

show subpopulations

Gnomad4 AFR exome

AF:

0.0443

Gnomad4 AMR exome

AF:

0.270

Gnomad4 ASJ exome

AF:

0.224

Gnomad4 EAS exome

AF:

0.509

Gnomad4 SAS exome

AF:

0.168

Gnomad4 FIN exome

AF:

0.192

Gnomad4 NFE exome

AF:

0.189

Gnomad4 OTH exome

AF:

0.202

GnomAD4 genome

AF:

0.162

AC:

24710

AN:

152212

Hom.:

2668

Cov.:

AF XY:

0.165

AC XY:

12276

AN XY:

74418

show subpopulations

Gnomad4 AFR

AF:

0.0490

Gnomad4 AMR

AF:

0.201

Gnomad4 ASJ

AF:

0.225

Gnomad4 EAS

AF:

0.500

Gnomad4 SAS

AF:

0.186

Gnomad4 FIN

AF:

0.202

Gnomad4 NFE

AF:

0.187

Gnomad4 OTH

AF:

0.169

Alfa

AF:

0.168

Hom.:

1269

Bravo

AF:

0.162

Asia WGS

AF:

0.302

AC:

1049

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

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

-0.81

CADD

Benign

4.7

DANN

Benign

0.78

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over