chr5-71461958-C-CTTTT

Variant names:

• chr5-71461958-C-CTTTT
• rs370261571
• NM_018429.3:c.599+50_599+53dupTTTT

Variant summary

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

The NM_018429.3(BDP1):​c.599+50_599+53dupTTTT 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 0.00063 (0 hom., cov: 0)
  • Exomes 𝑓: 0.0030 (1 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: PanelApp Australia, 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+50_599+53dupTTTT		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+33insTTTT		intron	N/A	ENSP00000351575.4	A6H8Y1-1
	BDP1	ENST00000508917.6	TSL:1	n.791+32_791+33insTTTT		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.000633 AC: 69 AN: 109042 Hom.: 0 Cov.: 0

Gnomad AFR AF: 0.000658

Gnomad AMI AF: 0.00119

Gnomad AMR AF: 0.000990

Gnomad ASJ AF: 0.000984

Gnomad EAS AF: 0.000266

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.000441

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000628

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.00298 AC: 994 AN: 333658 Hom.: 1 Cov.: 0 AF XY: 0.00286 AC XY: 523 AN XY: 182982

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

African (AFR) AF: 0.00402 AC: 34 AN: 8468

American (AMR) AF: 0.00345 AC: 54 AN: 15646

Ashkenazi Jewish (ASJ) AF: 0.00345 AC: 30 AN: 8708

East Asian (EAS) AF: 0.00231 AC: 38 AN: 16426

South Asian (SAS) AF: 0.00449 AC: 186 AN: 41434

European-Finnish (FIN) AF: 0.00177 AC: 37 AN: 20916

Middle Eastern (MID) AF: 0.00360 AC: 4 AN: 1112

European-Non Finnish (NFE) AF: 0.00276 AC: 566 AN: 204732

Other (OTH) AF: 0.00278 AC: 45 AN: 16216

⚠️ 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: 0.000633 AC: 69 AN: 109026 Hom.: 0 Cov.: 0 AF XY: 0.000768 AC XY: 38 AN XY: 49490

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

African (AFR) AF: 0.000658 AC: 19 AN: 28896

American (AMR) AF: 0.000990 AC: 8 AN: 8080

Ashkenazi Jewish (ASJ) AF: 0.000984 AC: 3 AN: 3048

East Asian (EAS) AF: 0.000267 AC: 1 AN: 3742

South Asian (SAS) AF: 0.00 AC: 0 AN: 3268

European-Finnish (FIN) AF: 0.000441 AC: 1 AN: 2270

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 150

European-Non Finnish (NFE) AF: 0.000628 AC: 36 AN: 57302

Other (OTH) AF: 0.00 AC: 0 AN: 1430

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5. (p-value = 0.00000000000520761), which strongly suggests a high chance of mosaicism in these individuals.

Alfa AF: 0.00357 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;