rs7964223

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_ModerateBA1

The NM_002273.4(KRT8):​c.324+1122C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.366 in 152,102 control chromosomes in the GnomAD database, including 10,515 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 0.37 ( 10514 hom., cov: 32)
Exomes 𝑓: 0.39 ( 1 hom. )

Consequence

KRT8
NM_002273.4 intron

Scores

2

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 2.17
Variant links:
Genes affected
KRT8 (HGNC:6446): (keratin 8) This gene is a member of the type II keratin family clustered on the long arm of chromosome 12. Type I and type II keratins heteropolymerize to form intermediate-sized filaments in the cytoplasm of epithelial cells. The product of this gene typically dimerizes with keratin 18 to form an intermediate filament in simple single-layered epithelial cells. This protein plays a role in maintaining cellular structural integrity and also functions in signal transduction and cellular differentiation. Mutations in this gene cause cryptogenic cirrhosis. Alternatively spliced transcript variants have been found for this gene. [provided by RefSeq, Jan 2012]

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -10 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.31).
BA1
GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.402 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
KRT8NM_002273.4 linkuse as main transcriptc.324+1122C>T intron_variant ENST00000692008.1
KRT8NM_001256282.2 linkuse as main transcriptc.408+1122C>T intron_variant
KRT8NM_001256293.2 linkuse as main transcriptc.324+1122C>T intron_variant
KRT8NR_045962.2 linkuse as main transcriptn.775+1122C>T intron_variant, non_coding_transcript_variant

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
KRT8ENST00000692008.1 linkuse as main transcriptc.324+1122C>T intron_variant NM_002273.4 P2P05787-1

Frequencies

GnomAD3 genomes
AF:
0.366
AC:
55567
AN:
151956
Hom.:
10489
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.382
Gnomad AMI
AF:
0.525
Gnomad AMR
AF:
0.298
Gnomad ASJ
AF:
0.324
Gnomad EAS
AF:
0.137
Gnomad SAS
AF:
0.321
Gnomad FIN
AF:
0.276
Gnomad MID
AF:
0.424
Gnomad NFE
AF:
0.406
Gnomad OTH
AF:
0.356
GnomAD4 exome
AF:
0.393
AC:
11
AN:
28
Hom.:
1
Cov.:
0
AF XY:
0.444
AC XY:
8
AN XY:
18
show subpopulations
Gnomad4 FIN exome
AF:
0.333
Gnomad4 NFE exome
AF:
0.400
Gnomad4 OTH exome
AF:
0.500
GnomAD4 genome
AF:
0.366
AC:
55637
AN:
152074
Hom.:
10514
Cov.:
32
AF XY:
0.358
AC XY:
26583
AN XY:
74342
show subpopulations
Gnomad4 AFR
AF:
0.382
Gnomad4 AMR
AF:
0.299
Gnomad4 ASJ
AF:
0.324
Gnomad4 EAS
AF:
0.137
Gnomad4 SAS
AF:
0.322
Gnomad4 FIN
AF:
0.276
Gnomad4 NFE
AF:
0.406
Gnomad4 OTH
AF:
0.357
Alfa
AF:
0.395
Hom.:
17456
Bravo
AF:
0.369
Asia WGS
AF:
0.231
AC:
802
AN:
3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.31
CADD
Benign
18
DANN
Benign
0.93

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.

Other links and lift over

dbSNP: rs7964223; hg19: chr12-53297320; COSMIC: COSV53178584; COSMIC: COSV53178584; API