5-71463493-A-T

Variant names:

• chr5-71463493-A-T
• rs1017225
• NM_018429.3:c.600-565A>T

Variant summary

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

The NM_018429.3(BDP1):​c.600-565A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.301 in 151,890 control chromosomes in the GnomAD database, including 7,947 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 0.30 (7947 hom., cov: 31)
• Consequence: BDP1 NM_018429.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.364

Genes affected

BDP1 (HGNC:13652): (B double prime 1, subunit of RNA polymerase III transcription initiation factor IIIB) The product of this gene is a subunit of the TFIIIB transcription initiation complex, which recruits RNA polymerase III to target promoters in order to initiate transcription. The encoded protein localizes to concentrated aggregates in the nucleus, and is required for transcription from all three types of polymerase III promoters. It is phosphorylated by casein kinase II during mitosis, resulting in its release from chromatin and suppression of polymerase III transcription. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.487 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
BDP1	NM_018429.3	c.600-565A>T		intron_variant	Intron 3 of 38	ENST00000358731.9	NP_060899.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
BDP1	ENST00000358731.9	c.600-565A>T		intron_variant	Intron 3 of 38	1	NM_018429.3	ENSP00000351575.4
BDP1	ENST00000508917.6	n.792-565A>T		intron_variant	Intron 3 of 31	1

Frequencies

GnomAD3 genomes AF: 0.301 AC: 45661 AN: 151772 Hom.: 7942 Cov.: 31

Gnomad AFR AF: 0.137

Gnomad AMI AF: 0.179

Gnomad AMR AF: 0.481

Gnomad ASJ AF: 0.415

Gnomad EAS AF: 0.503

Gnomad SAS AF: 0.291

Gnomad FIN AF: 0.277

Gnomad MID AF: 0.401

Gnomad NFE AF: 0.343

Gnomad OTH AF: 0.338

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

GnomAD4 genome AF: 0.301 AC: 45672 AN: 151890 Hom.: 7947 Cov.: 31 AF XY: 0.303 AC XY: 22453 AN XY: 74222

Gnomad4 AFR AF: 0.136

Gnomad4 AMR AF: 0.482

Gnomad4 ASJ AF: 0.415

Gnomad4 EAS AF: 0.503

Gnomad4 SAS AF: 0.292

Gnomad4 FIN AF: 0.277

Gnomad4 NFE AF: 0.343

Gnomad4 OTH AF: 0.336

Alfa AF: 0.310 Hom.: 969

Bravo AF: 0.316

Asia WGS AF: 0.365 AC: 1270 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	1.0
DANN	Benign	0.80

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs1017225; hg19: chr5-70759320; COSMIC: COSV62429987;