5-71461958-CTTTTTTTTTTTTT-CTTTTTTTTTTTTTTTTTTTTT

Variant names:

• chr5-71461958-C-CTTTTTTTT
• rs370261571
• NM_018429.3:c.599+46_599+53dupTTTTTTTT

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 0P and 0B.

The NM_018429.3(BDP1):​c.599+46_599+53dupTTTTTTTT variant causes a intron change involving the alteration of a non-conserved nucleotide. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.000073 (0 hom., cov: 0)
  • Exomes 𝑓: 0.000036 (0 hom.)
• Consequence: BDP1 NM_018429.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.304
• Publications: 0 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: Uncertain_significance. The variant received 0 ACMG points.

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.599+46_599+53dupTTTTTTTT		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.599+32_599+33insTTTTTTTT		intron	N/A	ENSP00000351575.4	A6H8Y1-1
	BDP1	ENST00000508917.6	TSL:1	n.791+32_791+33insTTTTTTTT		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.0000733 AC: 8 AN: 109072 Hom.: 0 Cov.: 0

Gnomad AFR AF: 0.0000347

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000124

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000266

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000872

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.0000358 AC: 12 AN: 335034 Hom.: 0 Cov.: 0 AF XY: 0.0000272 AC XY: 5 AN XY: 183732

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

African (AFR) AF: 0.000117 AC: 1 AN: 8512

American (AMR) AF: 0.00 AC: 0 AN: 15734

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 8760

East Asian (EAS) AF: 0.00 AC: 0 AN: 16476

South Asian (SAS) AF: 0.0000480 AC: 2 AN: 41680

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 20974

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 1122

European-Non Finnish (NFE) AF: 0.0000438 AC: 9 AN: 205496

Other (OTH) AF: 0.00 AC: 0 AN: 16280

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome AF: 0.0000733 AC: 8 AN: 109072 Hom.: 0 Cov.: 0 AF XY: 0.000101 AC XY: 5 AN XY: 49496

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

African (AFR) AF: 0.0000347 AC: 1 AN: 28858

American (AMR) AF: 0.000124 AC: 1 AN: 8080

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3050

East Asian (EAS) AF: 0.000266 AC: 1 AN: 3758

South Asian (SAS) AF: 0.00 AC: 0 AN: 3290

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 2272

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 164

European-Non Finnish (NFE) AF: 0.0000872 AC: 5 AN: 57332

Other (OTH) AF: 0.00 AC: 0 AN: 1426

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5. (p-value = 0.0000000411224), which strongly suggests a high chance of mosaicism in these individuals.

Alfa AF: 0.00160 Hom.: 909

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.30

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs370261571; hg19: chr5-70757785;