5-71552687-T-G

Variant names:

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

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_018429.3(BDP1):​c.6996-429T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.011 in 125,770 control chromosomes in the GnomAD database, with no homozygous occurrence. 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 0.011 (0 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Variant has high frequency in the AFR (0.0284) population. However there is too low homozygotes in high coverage region: (expected more than 3, got 0).
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.96).

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>G		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>G		intron	N/A	ENSP00000351575.4
	BDP1	ENST00000525844.1	TSL:1	n.1062-429T>G		intron	N/A	ENSP00000432404.1
	BDP1	ENST00000514903.7	TSL:5	n.1574-429T>G		intron	N/A	ENSP00000421910.3

Frequencies

GnomAD3 genomes AF: 0.0110 AC: 1384 AN: 125678 Hom.: 0 Cov.: 34

Gnomad AFR AF: 0.0300

Gnomad AMI AF: 0.00424

Gnomad AMR AF: 0.00701

Gnomad ASJ AF: 0.00292

Gnomad EAS AF: 0.0220

Gnomad SAS AF: 0.0126

Gnomad FIN AF: 0.00531

Gnomad MID AF: 0.00725

Gnomad NFE AF: 0.00302

Gnomad OTH AF: 0.00964

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

GnomAD4 genome AF: 0.0110 AC: 1388 AN: 125770 Hom.: 0 Cov.: 34 AF XY: 0.0113 AC XY: 695 AN XY: 61616

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.0300 AC: 896 AN: 29876

American (AMR) AF: 0.00700 AC: 94 AN: 13424

Ashkenazi Jewish (ASJ) AF: 0.00292 AC: 9 AN: 3080

East Asian (EAS) AF: 0.0220 AC: 88 AN: 4000

South Asian (SAS) AF: 0.0123 AC: 50 AN: 4052

European-Finnish (FIN) AF: 0.00531 AC: 46 AN: 8670

Middle Eastern (MID) AF: 0.00781 AC: 2 AN: 256

European-Non Finnish (NFE) AF: 0.00302 AC: 181 AN: 59924

Other (OTH) AF: 0.0107 AC: 19 AN: 1780

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5. (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

Alfa AF: 0.00 Hom.: 8

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	4.9
DANN	Benign	0.36
PhyloP100		0.065
Mutation Taster		=100/0	polymorphism

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: rs467880; hg19: chr5-70848514;