rs7623808

Variant names:

• chr3-67010865-G-T
• rs7623808
• NM_032505.3:c.*2480G>T

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 5 publications found

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]

KBTBD8 Gene-Disease associations (from GenCC):

• Tourette syndrome

  Inheritance: Unknown Classification: NO_KNOWN Submitted by: Labcorp Genetics (formerly Invitae)

ACMG classification

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
KBTBD8	NM_032505.3	c.*2480G>T		3_prime_UTR_variant	Exon 4 of 4	ENST00000417314.2	NP_115894.2
KBTBD8	XM_005264771.4	c.*2480G>T		3_prime_UTR_variant	Exon 3 of 3		XP_005264828.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
KBTBD8	ENST00000417314.2	c.*2480G>T		3_prime_UTR_variant	Exon 4 of 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

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AF: 0.162 AC: 69 AN: 426

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 2

Other (OTH) AF: 0.500 AC: 2 AN: 4

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

African (AFR) AF: 0.252 AC: 10456 AN: 41456

American (AMR) AF: 0.199 AC: 3047 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.122 AC: 422 AN: 3468

East Asian (EAS) AF: 0.0276 AC: 143 AN: 5184

South Asian (SAS) AF: 0.114 AC: 549 AN: 4816

European-Finnish (FIN) AF: 0.170 AC: 1801 AN: 10576

Middle Eastern (MID) AF: 0.0952 AC: 28 AN: 294

European-Non Finnish (NFE) AF: 0.136 AC: 9224 AN: 67964

Other (OTH) AF: 0.167 AC: 352 AN: 2108

Alfa AF: 0.158 Hom.: 1016

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
PhyloP100		0.76
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

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