Variant chr12-52361405-A-G 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 NM_002283.4(KRT85):c.1330+62T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.172 in 1,494,054 control chromosomes in the GnomAD database, including 23,364 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.17 ( 2338 hom., cov: 33)

Exomes 𝑓: 0.17 ( 21026 hom. )

Consequence

KRT85
NM_002283.4 intron

Scores

Clinical Significance

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

Conservation

PhyloP100: -0.638

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=-0.9).

BP6

Variant 12-52361405-A-G is Benign according to our data. Variant chr12-52361405-A-G is described in ClinVar as [Benign]. Clinvar id is 1288804.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.251 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.1330+62T>C		intron_variant		ENST00000257901.7	NP_002274.1
KRT85	NM_001300810.1 linkuse as main transcript	c.694+62T>C		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.1330+62T>C		intron_variant		1	NM_002283.4	ENSP00000257901	P1
KRT85	ENST00000544265.1 linkuse as main transcript	c.694+62T>C		intron_variant		2		ENSP00000440240

Frequencies

GnomAD3 genomes

AF:

0.168

AC:

25588

AN:

152120

Hom.:

2335

Cov.:

show subpopulations

Gnomad AFR

AF:

0.122

Gnomad AMI

AF:

0.176

Gnomad AMR

AF:

0.257

Gnomad ASJ

AF:

0.123

Gnomad EAS

AF:

0.152

Gnomad SAS

AF:

0.153

Gnomad FIN

AF:

0.209

Gnomad MID

AF:

0.0981

Gnomad NFE

AF:

0.175

Gnomad OTH

AF:

0.170

GnomAD4 exome

AF:

0.173

AC:

232115

AN:

1341816

Hom.:

21026

AF XY:

0.172

AC XY:

115897

AN XY:

674760

show subpopulations

Gnomad4 AFR exome

AF:

0.116

Gnomad4 AMR exome

AF:

0.297

Gnomad4 ASJ exome

AF:

0.122

Gnomad4 EAS exome

AF:

0.157

Gnomad4 SAS exome

AF:

0.149

Gnomad4 FIN exome

AF:

0.207

Gnomad4 NFE exome

AF:

0.172

Gnomad4 OTH exome

AF:

0.161

GnomAD4 genome

AF:

0.168

AC:

25601

AN:

152238

Hom.:

2338

Cov.:

AF XY:

0.171

AC XY:

12762

AN XY:

74432

show subpopulations

Gnomad4 AFR

AF:

0.122

Gnomad4 AMR

AF:

0.258

Gnomad4 ASJ

AF:

0.123

Gnomad4 EAS

AF:

0.152

Gnomad4 SAS

AF:

0.152

Gnomad4 FIN

AF:

0.209

Gnomad4 NFE

AF:

0.175

Gnomad4 OTH

AF:

0.170

Alfa

AF:

0.170

Hom.:

2229

Bravo

AF:

0.168

Asia WGS

AF:

0.153

AC:

530

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

-0.90

CADD

Benign

0.91

DANN

Benign

0.56

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

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