15-83057427-A-G

Position:

• chr15-83057427-A-G

Variant summary

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

The ENST00000261721.9(BTBD1):​c.402-882T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.217 in 152,202 control chromosomes in the GnomAD database, including 4,103 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 0.22 (4103 hom., cov: 32)
• Consequence: BTBD1 ENST00000261721.9 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.695

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 (EAS) allele frequency at 95% confidence interval = 0.546 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
BTBD1	NM_025238.4	c.402-882T>C		intron_variant		ENST00000261721.9	NP_079514.1
LOC124903542	XR_007064742.1	n.1320-4060A>G		intron_variant, non_coding_transcript_variant
BTBD1	NM_001011885.2	c.402-882T>C		intron_variant			NP_001011885.1
BTBD1	XR_007064459.1	n.503-882T>C		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
BTBD1	ENST00000261721.9	c.402-882T>C		intron_variant		1	NM_025238.4	ENSP00000261721	P1
	ENST00000566841.1	n.735-45997A>G		intron_variant, non_coding_transcript_variant		5
	ENST00000568441.1	n.38-32894A>G		intron_variant, non_coding_transcript_variant		5
	ENST00000570202.1	n.63-4060A>G		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes AF: 0.217 AC: 33065 AN: 152084 Hom.: 4102 Cov.: 32

Gnomad AFR AF: 0.245

Gnomad AMI AF: 0.366

Gnomad AMR AF: 0.286

Gnomad ASJ AF: 0.136

Gnomad EAS AF: 0.563

Gnomad SAS AF: 0.123

Gnomad FIN AF: 0.206

Gnomad MID AF: 0.199

Gnomad NFE AF: 0.169

Gnomad OTH AF: 0.238

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.217 AC: 33080 AN: 152202 Hom.: 4103 Cov.: 32 AF XY: 0.221 AC XY: 16458 AN XY: 74420

Gnomad4 AFR AF: 0.245

Gnomad4 AMR AF: 0.286

Gnomad4 ASJ AF: 0.136

Gnomad4 EAS AF: 0.563

Gnomad4 SAS AF: 0.122

Gnomad4 FIN AF: 0.206

Gnomad4 NFE AF: 0.169

Gnomad4 OTH AF: 0.237

Alfa AF: 0.185 Hom.: 5556

Bravo AF: 0.230

Asia WGS AF: 0.306 AC: 1062 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	9.6
DANN	Benign	0.71

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: rs1568657; hg19: chr15-83726179;