3-67010865-G-T

Position:

• chr3-67010865-G-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_032505.3(KBTBD8):​c.*2480G>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.171 in 152,486 control chromosomes in the GnomAD database, including 2,468 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 0.17 (2462 hom., cov: 32)
  • Exomes 𝑓: 0.16 (6 hom.)
• Consequence: KBTBD8 NM_032505.3 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.759

Genes affected

KBTBD8 (HGNC:30691): (kelch repeat and BTB domain containing 8) Involved in neural crest cell development; neural crest formation; and protein monoubiquitination. Part of Cul3-RING ubiquitin ligase complex. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.64).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.248 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
KBTBD8	NM_032505.3	c.*2480G>T		3_prime_UTR_variant	4/4	ENST00000417314.2	NP_115894.2
KBTBD8	XM_005264771.4	c.*2480G>T		3_prime_UTR_variant	3/3		XP_005264828.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
KBTBD8	ENST00000417314.2	c.*2480G>T		3_prime_UTR_variant	4/4	2	NM_032505.3	ENSP00000401878.2

Frequencies

GnomAD3 genomes AF: 0.171 AC: 26026 AN: 151936 Hom.: 2451 Cov.: 32

Gnomad AFR AF: 0.252

Gnomad AMI AF: 0.0526

Gnomad AMR AF: 0.199

Gnomad ASJ AF: 0.122

Gnomad EAS AF: 0.0271

Gnomad SAS AF: 0.114

Gnomad FIN AF: 0.170

Gnomad MID AF: 0.0918

Gnomad NFE AF: 0.136

Gnomad OTH AF: 0.169

GnomAD4 exome AF: 0.164 AC: 71 AN: 432 Hom.: 6 Cov.: 0 AF XY: 0.158 AC XY: 41 AN XY: 260

Gnomad4 FIN exome AF: 0.162

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.500

GnomAD4 genome AF: 0.171 AC: 26070 AN: 152054 Hom.: 2462 Cov.: 32 AF XY: 0.170 AC XY: 12652 AN XY: 74332

Gnomad4 AFR AF: 0.252

Gnomad4 AMR AF: 0.199

Gnomad4 ASJ AF: 0.122

Gnomad4 EAS AF: 0.0276

Gnomad4 SAS AF: 0.114

Gnomad4 FIN AF: 0.170

Gnomad4 NFE AF: 0.136

Gnomad4 OTH AF: 0.167

Alfa AF: 0.157 Hom.: 866

Bravo AF: 0.180

Asia WGS AF: 0.0840 AC: 291 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.64
CADD	Benign	6.9
DANN	Benign	0.77

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

Other links and lift over

dbSNP: rs7623808; hg19: chr3-67061289; COSMIC: COSV55131693; COSMIC: COSV55131693;