chr5-71463493-A-T

Variant names:

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

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 2 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=-0.89).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.487 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.600-565A>T		intron	N/A	NP_060899.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	BDP1	ENST00000358731.9	TSL:1 MANE Select	c.600-565A>T		intron	N/A	ENSP00000351575.4
	BDP1	ENST00000508917.6	TSL:1	n.792-565A>T		intron	N/A

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

African (AFR) AF: 0.136 AC: 5655 AN: 41440

American (AMR) AF: 0.482 AC: 7345 AN: 15238

Ashkenazi Jewish (ASJ) AF: 0.415 AC: 1439 AN: 3464

East Asian (EAS) AF: 0.503 AC: 2592 AN: 5152

South Asian (SAS) AF: 0.292 AC: 1406 AN: 4816

European-Finnish (FIN) AF: 0.277 AC: 2911 AN: 10524

Middle Eastern (MID) AF: 0.397 AC: 116 AN: 292

European-Non Finnish (NFE) AF: 0.343 AC: 23338 AN: 67946

Other (OTH) AF: 0.336 AC: 707 AN: 2106

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 v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	1.0
DANN	Benign	0.80
PhyloP100		-0.36
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs1017225; hg19: chr5-70759320; COSMIC: COSV62429987;