Variant 13-70107466-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6BP7BA1

The NM_020866.3(KLHL1):c.234A>G(p.Ser78Ser) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0792 in 1,613,850 control chromosomes in the GnomAD database, including 8,263 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (no stars).

Frequency

Genomes: 𝑓 0.12 ( 1610 hom., cov: 32)

Exomes 𝑓: 0.075 ( 6653 hom. )

Consequence

KLHL1
NM_020866.3 synonymous

Scores

Clinical Significance

Benign no assertion criteria provided B:1

Conservation

PhyloP100: -4.97

Variant links:

Genes affected

KLHL1 (HGNC:6352): (kelch like family member 1) The KLHL1 protein belongs to a family of actin-organizing proteins related to Drosophila Kelch (Nemes et al., 2000 [PubMed 10888605]).[supplied by OMIM, Feb 2010]

KLHL1 links:

ATXN8OS (HGNC:10561): (ATXN8 opposite strand lncRNA) This gene is an antisense transcript to the KLHL1 gene (homolog to the Drosophila KELCH gene); it does not itself appear to be protein coding. A TAC/TGC trinucleotide repeat expansion that is incorporated into this gene transcript, but not the KLHL1 transcript, causes spinocerebellar ataxia type 8. Presumably the expansion interferes with normal antisense function of this transcript. [provided by RefSeq, Oct 2008]

ATXN8OS links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -14 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.99).

BP6

Variant 13-70107466-T-C is Benign according to our data. Variant chr13-70107466-T-C is described in ClinVar as [Benign]. Clinvar id is 3059673.Status of the report is no_assertion_criteria_provided, 0 stars.

BP7

Synonymous conserved (PhyloP=-4.97 with no splicing effect.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.31 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
KLHL1	NM_020866.3 link	c.234A>G	p.Ser78Ser	synonymous_variant	Exon 1 of 11	ENST00000377844.9	NP_065917.1	Q9NR64Q8TBJ7
KLHL1	NM_001286725.2 link	c.234A>G	p.Ser78Ser	synonymous_variant	Exon 1 of 10		NP_001273654.1	Q9NR64F5H1J3Q8TBJ7B7Z3I8
ATXN8OS	NR_002717.3 link	n.46T>C		non_coding_transcript_exon_variant	Exon 1 of 5
ATXN8OS	NR_185842.1 link	n.46T>C		non_coding_transcript_exon_variant	Exon 1 of 4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
KLHL1	ENST00000377844.9 link	c.234A>G	p.Ser78Ser	synonymous_variant	Exon 1 of 11	1	NM_020866.3	ENSP00000367075.4	Q9NR64
KLHL1	ENST00000545028.2 link	c.234A>G	p.Ser78Ser	synonymous_variant	Exon 1 of 10	2		ENSP00000439602.2	F5H1J3
ATXN8OS	ENST00000414504.6 link	n.254T>C		non_coding_transcript_exon_variant	Exon 1 of 5	5
ATXN8OS	ENST00000665905.1 link	n.138T>C		non_coding_transcript_exon_variant	Exon 1 of 4

Frequencies

GnomAD3 genomes

AF:

0.119

AC:

18087

AN:

151904

Hom.:

1600

Cov.:

show subpopulations

Gnomad AFR

AF:

0.216

Gnomad AMI

AF:

0.0110

Gnomad AMR

AF:

0.0974

Gnomad ASJ

AF:

0.0210

Gnomad EAS

AF:

0.322

Gnomad SAS

AF:

0.116

Gnomad FIN

AF:

0.129

Gnomad MID

AF:

0.0316

Gnomad NFE

AF:

0.0560

Gnomad OTH

AF:

0.0874

GnomAD3 exomes

AF:

0.111

AC:

27586

AN:

249300

Hom.:

2302

AF XY:

0.104

AC XY:

14058

AN XY:

134946

show subpopulations

Gnomad AFR exome

AF:

0.219

Gnomad AMR exome

AF:

0.142

Gnomad ASJ exome

AF:

0.0230

Gnomad EAS exome

AF:

0.322

Gnomad SAS exome

AF:

0.108

Gnomad FIN exome

AF:

0.119

Gnomad NFE exome

AF:

0.0589

Gnomad OTH exome

AF:

0.0809

GnomAD4 exome

AF:

0.0750

AC:

109658

AN:

1461830

Hom.:

6653

Cov.:

AF XY:

0.0748

AC XY:

54397

AN XY:

727226

show subpopulations

Gnomad4 AFR exome

AF:

0.221

Gnomad4 AMR exome

AF:

0.137

Gnomad4 ASJ exome

AF:

0.0233

Gnomad4 EAS exome

AF:

0.352

Gnomad4 SAS exome

AF:

0.103

Gnomad4 FIN exome

AF:

0.119

Gnomad4 NFE exome

AF:

0.0551

Gnomad4 OTH exome

AF:

0.0796

GnomAD4 genome

AF:

0.119

AC:

18121

AN:

152020

Hom.:

1610

Cov.:

AF XY:

0.122

AC XY:

9084

AN XY:

74294

show subpopulations

Gnomad4 AFR

AF:

0.216

Gnomad4 AMR

AF:

0.0978

Gnomad4 ASJ

AF:

0.0210

Gnomad4 EAS

AF:

0.323

Gnomad4 SAS

AF:

0.115

Gnomad4 FIN

AF:

0.129

Gnomad4 NFE

AF:

0.0560

Gnomad4 OTH

AF:

0.0880

Alfa

AF:

0.0757

Hom.:

339

Bravo

AF:

0.125

Asia WGS

AF:

0.204

AC:

709

AN:

3478

EpiCase

AF:

0.0469

EpiControl

AF:

0.0479

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

KLHL1-related disorder

Benign:1

Benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Jul 18, 2019

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.99

CADD

Benign

0.053

DANN

Benign

0.34

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