5-71461958-CTTTTTTTTTTTTT-CTTTTTTTTTTTTTTTTTTTTTTTTT

Variant names:

• chr5-71461958-C-CTTTTTTTTTTTT
• rs370261571
• NM_018429.3:c.599+42_599+53dupTTTTTTTTTTTT

Variant summary

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

The NM_018429.3(BDP1):​c.599+42_599+53dupTTTTTTTTTTTT variant causes a intron change involving the alteration of a non-conserved nucleotide. It is difficult to determine the true allele frequency of this variant because it is of type INS_BIG, and the frequency of such variant types in population databases may be underestimated and unreliable. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.0000092 (0 hom., cov: 0)
  • Exomes 𝑓: 0.0000060 (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+42_599+53dupTTTTTTTTTTTT		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+33insTTTTTTTTTTTT		intron	N/A	ENSP00000351575.4	A6H8Y1-1
	BDP1	ENST00000508917.6	TSL:1	n.791+32_791+33insTTTTTTTTTTTT		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.00000917 AC: 1 AN: 109076 Hom.: 0 Cov.: 0

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.000701

GnomAD4 exome AF: 0.00000597 AC: 2 AN: 335042 Hom.: 0 Cov.: 0 AF XY: 0.00000544 AC XY: 1 AN XY: 183736

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

African (AFR) AF: 0.00 AC: 0 AN: 8514

American (AMR) AF: 0.00 AC: 0 AN: 15736

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

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

South Asian (SAS) AF: 0.00 AC: 0 AN: 41682

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: 0.00000973 AC: 2 AN: 205498

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

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0.0000000000983081), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome AF: 0.00000917 AC: 1 AN: 109076 Hom.: 0 Cov.: 0 AF XY: 0.00 AC XY: 0 AN XY: 49498

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

African (AFR) AF: 0.00 AC: 0 AN: 28858

American (AMR) AF: 0.00 AC: 0 AN: 8082

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

East Asian (EAS) AF: 0.00 AC: 0 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: 0.00 AC: 0 AN: 57334

Other (OTH) AF: 0.000701 AC: 1 AN: 1426

⚠️ 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.

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;