15-83016562-A-T

Variant summary

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

The NM_025238.4(BTBD1):c.*1505T>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.188 in 151,992 control chromosomes in the GnomAD database, including 2,871 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 0.19 (2871 hom., cov: 32)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: BTBD1 NM_025238.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.97

Genes affected

BTBD1 (HGNC:1120): (BTB domain containing 1) The C-terminus of the protein encoded by this gene binds topoisomerase I. The N-terminus contains a proline-rich region and a BTB/POZ domain (broad-complex, Tramtrack and bric a brac/Pox virus and Zinc finger), both of which are typically involved in protein-protein interactions. Subcellularly, the protein localizes to cytoplasmic bodies. Alternative splicing results in multiple transcript variants encoding different isoforms. [provided by RefSeq, Jul 2008]

(HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.212 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
BTBD1	NM_025238.4	c.*1505T>A		3_prime_UTR_variant	8/8	ENST00000261721.9
LOC124903542	XR_007064742.1	n.1319+3503A>T		intron_variant, non_coding_transcript_variant
BTBD1	NM_001011885.2	c.*1708T>A		3_prime_UTR_variant	7/7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
BTBD1	ENST00000261721.9	c.*1505T>A		3_prime_UTR_variant	8/8	1	NM_025238.4	P1
	ENST00000566841.1	n.735-86862A>T		intron_variant, non_coding_transcript_variant		5
	ENST00000570202.1	n.62+3840A>T		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes AF: 0.188 AC: 28552 AN: 151874 Hom.: 2870 Cov.: 32

Gnomad AFR AF: 0.164

Gnomad AMI AF: 0.163

Gnomad AMR AF: 0.208

Gnomad ASJ AF: 0.257

Gnomad EAS AF: 0.00385

Gnomad SAS AF: 0.102

Gnomad FIN AF: 0.190

Gnomad MID AF: 0.142

Gnomad NFE AF: 0.215

Gnomad OTH AF: 0.183

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 2 Hom.: 0 Cov.: 0 AF XY: 0.00 AC XY: 0 AN XY: 2

Gnomad4 NFE exome AF: 0.00

GnomAD4 genome AF: 0.188 AC: 28574 AN: 151992 Hom.: 2871 Cov.: 32 AF XY: 0.181 AC XY: 13473 AN XY: 74310

Gnomad4 AFR AF: 0.163

Gnomad4 AMR AF: 0.209

Gnomad4 ASJ AF: 0.257

Gnomad4 EAS AF: 0.00386

Gnomad4 SAS AF: 0.102

Gnomad4 FIN AF: 0.190

Gnomad4 NFE AF: 0.215

Gnomad4 OTH AF: 0.180

Alfa AF: 0.113 Hom.: 163

Bravo AF: 0.191

Asia WGS AF: 0.0760 AC: 264 AN: 3468

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
Cadd	Benign	5.3
Dann	Benign	0.70
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

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: rs1045742; hg19: chr15-83685314;