19-2028986-T-C

Variant names:

• chr19-2028986-T-C
• rs7257116
• ENST00000590646.5:c.-282-152A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000590646.5(BTBD2):​c.-282-152A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.7 in 152,020 control chromosomes in the GnomAD database, including 38,446 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 0.70 (38446 hom., cov: 31)
• Consequence: BTBD2 ENST00000590646.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.987
• Publications: 11 publications found

Genes affected

BTBD2 (HGNC:15504): (BTB domain containing 2) 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. [provided by RefSeq, Jul 2008]

LOC107985278 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.98).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.884 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LOC107985278	XR_001753845.2	n.132-152A>G		intron_variant	Intron 1 of 3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
BTBD2	ENST00000590646.5	c.-282-152A>G		intron_variant	Intron 1 of 4	4		ENSP00000481529.1
BTBD2	ENST00000587742.5	c.-332-152A>G		intron_variant	Intron 1 of 5	5		ENSP00000483892.1
BTBD2	ENST00000588395.1	c.-156+5765A>G		intron_variant	Intron 1 of 2	5		ENSP00000478992.1

Frequencies

GnomAD3 genomes AF: 0.699 AC: 106249 AN: 151902 Hom.: 38383 Cov.: 31

Gnomad AFR AF: 0.892

Gnomad AMI AF: 0.674

Gnomad AMR AF: 0.679

Gnomad ASJ AF: 0.605

Gnomad EAS AF: 0.682

Gnomad SAS AF: 0.620

Gnomad FIN AF: 0.574

Gnomad MID AF: 0.682

Gnomad NFE AF: 0.618

Gnomad OTH AF: 0.706

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

GnomAD4 genome AF: 0.700 AC: 106372 AN: 152020 Hom.: 38446 Cov.: 31 AF XY: 0.696 AC XY: 51681 AN XY: 74290

African (AFR) AF: 0.892 AC: 37032 AN: 41518

American (AMR) AF: 0.679 AC: 10357 AN: 15254

Ashkenazi Jewish (ASJ) AF: 0.605 AC: 2099 AN: 3470

East Asian (EAS) AF: 0.682 AC: 3512 AN: 5152

South Asian (SAS) AF: 0.620 AC: 2989 AN: 4818

European-Finnish (FIN) AF: 0.574 AC: 6063 AN: 10556

Middle Eastern (MID) AF: 0.668 AC: 195 AN: 292

European-Non Finnish (NFE) AF: 0.618 AC: 42021 AN: 67944

Other (OTH) AF: 0.708 AC: 1489 AN: 2104

Alfa AF: 0.636 Hom.: 88015

Bravo AF: 0.719

Asia WGS AF: 0.699 AC: 2432 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	1.1
DANN	Benign	0.51
PhyloP100		-0.99

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs7257116; hg19: chr19-2028985;