rs2280231

Positions:

• chr11-47578886-C-T

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

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
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.0560

Genes affected

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

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]

ACMG classification

Verdict is Benign. Variant got -14 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_single_submitter, 1 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	UniProt
KBTBD4	NM_018095.6	c.19+47G>A		intron_variant		ENST00000430070.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
KBTBD4	ENST00000430070.7	c.19+47G>A		intron_variant		1	NM_018095.6

Frequencies

GnomAD3 genomes AF: 0.201 AC: 30437 AN: 151786 Hom.: 3863 Cov.: 31

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

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.: 40 AF XY: 0.268 AC XY: 185113 AN XY: 690046

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.: 31 AF XY: 0.196 AC XY: 14580 AN XY: 74224

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:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jun 23, 2018

- -

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

Other links and lift over

dbSNP: rs2280231; hg19: chr11-47600438; COSMIC: COSV55453654; COSMIC: COSV55453654;