15-83016562-A-T

Variant names:

• chr15-83016562-A-T
• rs1045742
• NM_025238.4:c.*1505T>A

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 6 publications found

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]

ENSG00000259805 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_025238.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	BTBD1	NM_025238.4	MANE Select	c.*1505T>A		3_prime_UTR	Exon 8 of 8	NP_079514.1	Q9H0C5-1
	BTBD1	NM_001011885.2		c.*1708T>A		3_prime_UTR	Exon 7 of 7	NP_001011885.1	Q9H0C5-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	BTBD1	ENST00000261721.9	TSL:1 MANE Select	c.*1505T>A		3_prime_UTR	Exon 8 of 8	ENSP00000261721.4	Q9H0C5-1
	BTBD1	ENST00000944296.1		c.*1505T>A		3_prime_UTR	Exon 9 of 9	ENSP00000614355.1
	BTBD1	ENST00000944299.1		c.*1505T>A		3_prime_UTR	Exon 9 of 9	ENSP00000614358.1

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

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) AC: 0 AN: 0

Middle Eastern (MID) AC: 0 AN: 0

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

Other (OTH) AC: 0 AN: 0

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

African (AFR) AF: 0.163 AC: 6776 AN: 41466

American (AMR) AF: 0.209 AC: 3191 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.257 AC: 892 AN: 3468

East Asian (EAS) AF: 0.00386 AC: 20 AN: 5180

South Asian (SAS) AF: 0.102 AC: 492 AN: 4820

European-Finnish (FIN) AF: 0.190 AC: 2006 AN: 10540

Middle Eastern (MID) AF: 0.153 AC: 45 AN: 294

European-Non Finnish (NFE) AF: 0.215 AC: 14622 AN: 67922

Other (OTH) AF: 0.180 AC: 381 AN: 2114

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 v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	5.3
DANN	Benign	0.70
PhyloP100		2.0
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
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: rs1045742; hg19: chr15-83685314;