rs7448990

Variant names:

• chr5-71458107-G-A
• rs7448990
• NM_018429.3:c.213-472G>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.213-472G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.464 in 151,988 control chromosomes in the GnomAD database, including 16,660 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 0.46 (16660 hom., cov: 32)
• Consequence: BDP1 NM_018429.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.41
• Publications: 4 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
• 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=-0.98).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.531 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_018429.3. 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
	BDP1	NM_018429.3	MANE Select	c.213-472G>A		intron	N/A	NP_060899.2	A6H8Y1-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	BDP1	ENST00000358731.9	TSL:1 MANE Select	c.213-472G>A		intron	N/A	ENSP00000351575.4	A6H8Y1-1
	BDP1	ENST00000508917.6	TSL:1	n.405-472G>A		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.465 AC: 70550 AN: 151870 Hom.: 16651 Cov.: 32

Gnomad AFR AF: 0.446

Gnomad AMI AF: 0.644

Gnomad AMR AF: 0.364

Gnomad ASJ AF: 0.473

Gnomad EAS AF: 0.371

Gnomad SAS AF: 0.548

Gnomad FIN AF: 0.532

Gnomad MID AF: 0.449

Gnomad NFE AF: 0.486

Gnomad OTH AF: 0.459

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

GnomAD4 genome AF: 0.464 AC: 70595 AN: 151988 Hom.: 16660 Cov.: 32 AF XY: 0.466 AC XY: 34597 AN XY: 74278

African (AFR) AF: 0.446 AC: 18508 AN: 41458

American (AMR) AF: 0.364 AC: 5552 AN: 15258

Ashkenazi Jewish (ASJ) AF: 0.473 AC: 1640 AN: 3466

East Asian (EAS) AF: 0.370 AC: 1918 AN: 5180

South Asian (SAS) AF: 0.548 AC: 2642 AN: 4820

European-Finnish (FIN) AF: 0.532 AC: 5594 AN: 10516

Middle Eastern (MID) AF: 0.446 AC: 131 AN: 294

European-Non Finnish (NFE) AF: 0.486 AC: 33055 AN: 67970

Other (OTH) AF: 0.458 AC: 968 AN: 2114

Alfa AF: 0.460 Hom.: 3515

Bravo AF: 0.445

Asia WGS AF: 0.449 AC: 1561 AN: 3472

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	4.2
DANN	Benign	0.58
PhyloP100		1.4
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: rs7448990; hg19: chr5-70753934;