Variant rs2280231 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_018095.6(KBTBD4):c.19+47G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.26 in 1,550,998 control chromosomes in the GnomAD database, including 55,810 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.20 ( 3863 hom., cov: 31)

Exomes 𝑓: 0.27 ( 51947 hom. )

Consequence

KBTBD4
NM_018095.6 intron

Scores

Clinical Significance

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

Conservation

PhyloP100: -0.0560

Variant links:

Genes affected

KBTBD4 (HGNC:23761): (kelch repeat and BTB domain containing 4)

KBTBD4 links:

NDUFS3 (HGNC:7710): (NADH:ubiquinone oxidoreductase core subunit S3) This gene encodes one of the iron-sulfur protein (IP) components of mitochondrial NADH:ubiquinone oxidoreductase (complex I). Mutations in this gene are associated with Leigh syndrome resulting from mitochondrial complex I deficiency.[provided by RefSeq, Apr 2009]

NDUFS3 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.84).

BP6

Variant 11-47578886-C-T is Benign according to our data. Variant chr11-47578886-C-T is described in ClinVar as [Benign]. Clinvar id is 1239179.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.275 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
KBTBD4	NM_018095.6 linkuse as main transcript	c.19+47G>A		intron_variant		ENST00000430070.7	NP_060565.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
KBTBD4	ENST00000430070.7 linkuse as main transcript	c.19+47G>A		intron_variant		1	NM_018095.6	ENSP00000415106		Q9NVX7-2

Frequencies

GnomAD3 genomes

AF:

0.201

AC:

30437

AN:

151786

Hom.:

3863

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0501

Gnomad AMI

AF:

0.186

Gnomad AMR

AF:

0.191

Gnomad ASJ

AF:

0.335

Gnomad EAS

AF:

0.285

Gnomad SAS

AF:

0.255

Gnomad FIN

AF:

0.186

Gnomad MID

AF:

0.224

Gnomad NFE

AF:

0.278

Gnomad OTH

AF:

0.252

GnomAD3 exomes

AF:

0.241

AC:

37435

AN:

155152

Hom.:

5108

AF XY:

0.250

AC XY:

20569

AN XY:

82290

show subpopulations

Gnomad AFR exome

AF:

0.0460

Gnomad AMR exome

AF:

0.142

Gnomad ASJ exome

AF:

0.331

Gnomad EAS exome

AF:

0.299

Gnomad SAS exome

AF:

0.270

Gnomad FIN exome

AF:

0.184

Gnomad NFE exome

AF:

0.286

Gnomad OTH exome

AF:

0.277

GnomAD4 exome

AF:

0.267

AC:

373575

AN:

1399090

Hom.:

51947

Cov.:

AF XY:

0.268

AC XY:

185113

AN XY:

690046

show subpopulations

Gnomad4 AFR exome

AF:

0.0434

Gnomad4 AMR exome

AF:

0.148

Gnomad4 ASJ exome

AF:

0.338

Gnomad4 EAS exome

AF:

0.240

Gnomad4 SAS exome

AF:

0.270

Gnomad4 FIN exome

AF:

0.187

Gnomad4 NFE exome

AF:

0.280

Gnomad4 OTH exome

AF:

0.264

GnomAD4 genome

AF:

0.200

AC:

30423

AN:

151908

Hom.:

3863

Cov.:

AF XY:

0.196

AC XY:

14580

AN XY:

74224

show subpopulations

Gnomad4 AFR

AF:

0.0500

Gnomad4 AMR

AF:

0.191

Gnomad4 ASJ

AF:

0.335

Gnomad4 EAS

AF:

0.285

Gnomad4 SAS

AF:

0.255

Gnomad4 FIN

AF:

0.186

Gnomad4 NFE

AF:

0.278

Gnomad4 OTH

AF:

0.249

Alfa

AF:

0.276

Hom.:

12842

Bravo

AF:

0.193

Asia WGS

AF:

0.238

AC:

828

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	clinical testing	GeneDx	Jun 23, 2018	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.84

CADD

Benign

6.0

DANN

Benign

0.83

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