rs7300941
Variant names:
Variant summary
Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1
The NM_002281.4(KRT81):c.901-28A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.507 in 1,612,936 control chromosomes in the GnomAD database, including 211,591 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).
Frequency
Genomes: 𝑓 0.51 ( 20103 hom., cov: 31)
Exomes 𝑓: 0.51 ( 191488 hom. )
Consequence
KRT81
NM_002281.4 intron
NM_002281.4 intron
Scores
2
Clinical Significance
Conservation
PhyloP100: -1.19
Genes affected
KRT81 (HGNC:6458): (keratin 81) 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, as well as KRTHB3 and KRTHB6, is found primarily in the hair cortex. Mutations in this gene and KRTHB6 have been observed in patients with a rare dominant hair disease, monilethrix. Some human genome assemblies (example T2T-CHM13) have a non-coding version of the gene due to the presence of a SNP that introduces a premature stop codon after codon 281. [provided by RefSeq, Jan 2024]
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]
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ACMG classification
Classification was made for transcript
Our verdict: Benign. The variant received -20 ACMG points.
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.88).
BP6
Variant 12-52287749-T-C is Benign according to our data. Variant chr12-52287749-T-C is described in ClinVar as [Benign]. Clinvar id is 1274144.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BA1
GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.559 is higher than 0.05.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
KRT81 | NM_002281.4 | c.901-28A>G | intron_variant | Intron 5 of 8 | ENST00000327741.9 | NP_002272.2 | ||
KRT86 | NM_001320198.2 | c.-5+11803T>C | intron_variant | Intron 2 of 10 | ENST00000423955.7 | NP_001307127.1 | ||
KRT86 | XM_005268866.5 | c.129+11803T>C | intron_variant | Intron 2 of 10 | XP_005268923.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
KRT81 | ENST00000327741.9 | c.901-28A>G | intron_variant | Intron 5 of 8 | 1 | NM_002281.4 | ENSP00000369349.4 | |||
KRT86 | ENST00000423955.7 | c.-5+11803T>C | intron_variant | Intron 2 of 10 | 2 | NM_001320198.2 | ENSP00000444533.1 | |||
KRT86 | ENST00000553310.6 | c.-4-14164T>C | intron_variant | Intron 1 of 2 | 4 | ENSP00000452237.3 |
Frequencies
GnomAD3 genomes AF: 0.509 AC: 77202AN: 151744Hom.: 20089 Cov.: 31 show subpopulations
GnomAD3 genomes
AF:
AC:
77202
AN:
151744
Hom.:
Cov.:
31
Gnomad AFR
AF:
Gnomad AMI
AF:
Gnomad AMR
AF:
Gnomad ASJ
AF:
Gnomad EAS
AF:
Gnomad SAS
AF:
Gnomad FIN
AF:
Gnomad MID
AF:
Gnomad NFE
AF:
Gnomad OTH
AF:
GnomAD2 exomes AF: 0.457 AC: 114592AN: 250810 AF XY: 0.461 show subpopulations
GnomAD2 exomes
AF:
AC:
114592
AN:
250810
AF XY:
Gnomad AFR exome
AF:
Gnomad AMR exome
AF:
Gnomad ASJ exome
AF:
Gnomad EAS exome
AF:
Gnomad FIN exome
AF:
Gnomad NFE exome
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Gnomad OTH exome
AF:
GnomAD4 exome AF: 0.506 AC: 739903AN: 1461074Hom.: 191488 Cov.: 62 AF XY: 0.504 AC XY: 366589AN XY: 726834 show subpopulations
GnomAD4 exome
AF:
AC:
739903
AN:
1461074
Hom.:
Cov.:
62
AF XY:
AC XY:
366589
AN XY:
726834
show subpopulations
African (AFR)
AF:
AC:
18994
AN:
33460
American (AMR)
AF:
AC:
14105
AN:
44676
Ashkenazi Jewish (ASJ)
AF:
AC:
12013
AN:
26132
East Asian (EAS)
AF:
AC:
8343
AN:
39692
South Asian (SAS)
AF:
AC:
37551
AN:
86234
European-Finnish (FIN)
AF:
AC:
28348
AN:
53402
Middle Eastern (MID)
AF:
AC:
2452
AN:
5768
European-Non Finnish (NFE)
AF:
AC:
588207
AN:
1111366
Other (OTH)
AF:
AC:
29890
AN:
60344
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.453
Heterozygous variant carriers
0
19974
39948
59922
79896
99870
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance
GnomAD4 genome AF: 0.509 AC: 77254AN: 151862Hom.: 20103 Cov.: 31 AF XY: 0.505 AC XY: 37491AN XY: 74226 show subpopulations
GnomAD4 genome
AF:
AC:
77254
AN:
151862
Hom.:
Cov.:
31
AF XY:
AC XY:
37491
AN XY:
74226
show subpopulations
African (AFR)
AF:
AC:
23383
AN:
41368
American (AMR)
AF:
AC:
6222
AN:
15272
Ashkenazi Jewish (ASJ)
AF:
AC:
1568
AN:
3468
East Asian (EAS)
AF:
AC:
1000
AN:
5142
South Asian (SAS)
AF:
AC:
2065
AN:
4810
European-Finnish (FIN)
AF:
AC:
5627
AN:
10546
Middle Eastern (MID)
AF:
AC:
125
AN:
294
European-Non Finnish (NFE)
AF:
AC:
35563
AN:
67940
Other (OTH)
AF:
AC:
1048
AN:
2110
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.501
Heterozygous variant carriers
0
1907
3814
5720
7627
9534
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance
Alfa
AF:
Hom.:
Bravo
AF:
Asia WGS
AF:
AC:
1294
AN:
3476
ClinVar
Significance: Benign
Submissions summary: Benign:2
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not provided Benign:2
-
Breakthrough Genomics, Breakthrough Genomics
Significance:Benign
Review Status:criteria provided, single submitter
Collection Method:not provided
- -
Jul 09, 2018
GeneDx
Significance:Benign
Review Status:criteria provided, single submitter
Collection Method:clinical testing
- -
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
DANN
Benign
PhyloP100
Splicing
Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at
Publications
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