chr5-71552687-T-C

Variant names:

• chr5-71552687-T-C
• rs467880
• NM_018429.3:c.6996-429T>C

Variant summary

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

The NM_018429.3(BDP1):​c.6996-429T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.311 in 138,298 control chromosomes in the GnomAD database, including 5,757 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 0.31 (5757 hom., cov: 34)
• Consequence: BDP1 NM_018429.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0650
• 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 (AMR) allele frequency at 95% confidence interval = 0.461 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	BDP1	NM_018429.3	MANE Select	c.6996-429T>C		intron	N/A	NP_060899.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	BDP1	ENST00000358731.9	TSL:1 MANE Select	c.6996-429T>C		intron	N/A	ENSP00000351575.4
	BDP1	ENST00000525844.1	TSL:1	n.1062-429T>C		intron	N/A	ENSP00000432404.1
	BDP1	ENST00000514903.7	TSL:5	n.1574-429T>C		intron	N/A	ENSP00000421910.3

Frequencies

GnomAD3 genomes AF: 0.311 AC: 43043 AN: 138184 Hom.: 5752 Cov.: 34

Gnomad AFR AF: 0.152

Gnomad AMI AF: 0.205

Gnomad AMR AF: 0.470

Gnomad ASJ AF: 0.411

Gnomad EAS AF: 0.452

Gnomad SAS AF: 0.293

Gnomad FIN AF: 0.310

Gnomad MID AF: 0.396

Gnomad NFE AF: 0.353

Gnomad OTH AF: 0.346

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

GnomAD4 genome AF: 0.311 AC: 43057 AN: 138298 Hom.: 5757 Cov.: 34 AF XY: 0.313 AC XY: 21162 AN XY: 67592

African (AFR) AF: 0.152 AC: 5543 AN: 36562

American (AMR) AF: 0.470 AC: 6776 AN: 14416

Ashkenazi Jewish (ASJ) AF: 0.411 AC: 1324 AN: 3222

East Asian (EAS) AF: 0.453 AC: 2201 AN: 4862

South Asian (SAS) AF: 0.295 AC: 1314 AN: 4458

European-Finnish (FIN) AF: 0.310 AC: 2787 AN: 8976

Middle Eastern (MID) AF: 0.395 AC: 109 AN: 276

European-Non Finnish (NFE) AF: 0.353 AC: 22185 AN: 62844

Other (OTH) AF: 0.343 AC: 666 AN: 1940

Alfa AF: 0.0267 Hom.: 8

Bravo AF: 0.316

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	5.6
DANN	Benign	0.32
PhyloP100		0.065
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs467880; hg19: chr5-70848514; COSMIC: COSV62430188;