rs468467

Variant names:

• chr5-71552679-G-A
• rs468467
• NM_018429.3:c.6996-437G>A

Variant summary

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

The NM_018429.3(BDP1):​c.6996-437G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.387 in 149,736 control chromosomes in the GnomAD database, including 9,046 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 0.39 (9046 hom., cov: 35)
• Consequence: BDP1 NM_018429.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0750
• Publications: 3 publications found

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]

BDP1 Gene-Disease associations (from GenCC):

• hearing loss, autosomal recessive

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
• hearing loss, autosomal recessive 112

  Inheritance: AR Classification: LIMITED Submitted by: Ambry Genetics, PanelApp Australia
• nonsyndromic genetic hearing loss

  Inheritance: AR Classification: LIMITED Submitted by: ClinGen

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.97).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.424 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
BDP1	NM_018429.3	c.6996-437G>A		intron_variant	Intron 34 of 38	ENST00000358731.9	NP_060899.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
BDP1	ENST00000358731.9	c.6996-437G>A		intron_variant	Intron 34 of 38	1	NM_018429.3	ENSP00000351575.4
BDP1	ENST00000525844.1	n.1062-437G>A		intron_variant	Intron 8 of 13	1		ENSP00000432404.1
BDP1	ENST00000514903.7	n.1574-437G>A		intron_variant	Intron 10 of 15	5		ENSP00000421910.3

Frequencies

GnomAD3 genomes AF: 0.387 AC: 57871 AN: 149622 Hom.: 9051 Cov.: 35

Gnomad AFR AF: 0.331

Gnomad AMI AF: 0.563

Gnomad AMR AF: 0.305

Gnomad ASJ AF: 0.423

Gnomad EAS AF: 0.318

Gnomad SAS AF: 0.427

Gnomad FIN AF: 0.450

Gnomad MID AF: 0.397

Gnomad NFE AF: 0.428

Gnomad OTH AF: 0.391

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

GnomAD4 genome AF: 0.387 AC: 57889 AN: 149736 Hom.: 9046 Cov.: 35 AF XY: 0.387 AC XY: 28327 AN XY: 73158

African (AFR) AF: 0.330 AC: 13488 AN: 40830

American (AMR) AF: 0.304 AC: 4609 AN: 15158

Ashkenazi Jewish (ASJ) AF: 0.423 AC: 1447 AN: 3424

East Asian (EAS) AF: 0.318 AC: 1621 AN: 5092

South Asian (SAS) AF: 0.427 AC: 1993 AN: 4672

European-Finnish (FIN) AF: 0.450 AC: 4673 AN: 10390

Middle Eastern (MID) AF: 0.397 AC: 115 AN: 290

European-Non Finnish (NFE) AF: 0.428 AC: 28641 AN: 66928

Other (OTH) AF: 0.390 AC: 810 AN: 2078

Alfa AF: 0.393 Hom.: 1006

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	3.5
DANN	Benign	0.96
PhyloP100		0.075
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: rs468467; hg19: chr5-70848506; COSMIC: COSV62434055;