5-71461958-CTTTTTTTTTTTTT-CTTTTTTTTTTTT

Variant names:

• chr5-71461958-CT-C
• rs370261571
• NM_018429.3:c.599+53delT

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP6_Moderate BA1

The NM_018429.3(BDP1):​c.599+53delT variant causes a intron change involving the alteration of a non-conserved nucleotide. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.032 (26 hom., cov: 0)
  • Exomes 𝑓: 0.11 (3 hom.)
• Consequence: BDP1 NM_018429.3 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• 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: Benign. The variant received -10 ACMG points.

• BP6: Variant 5-71461958-CT-C is Benign according to our data. Variant chr5-71461958-CT-C is described in ClinVar as Benign. ClinVar VariationId is 1245971.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.0614 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.599+53delT		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+33delT		intron	N/A	ENSP00000351575.4	A6H8Y1-1
	BDP1	ENST00000508917.6	TSL:1	n.791+33delT		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.0317 AC: 3449 AN: 108920 Hom.: 25 Cov.: 0

Gnomad AFR AF: 0.0395

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0328

Gnomad ASJ AF: 0.0223

Gnomad EAS AF: 0.0250

Gnomad SAS AF: 0.0689

Gnomad FIN AF: 0.0406

Gnomad MID AF: 0.0244

Gnomad NFE AF: 0.0266

Gnomad OTH AF: 0.0267

GnomAD2 exomes AF: 0.0968 AC: 4568 AN: 47180 AF XY: 0.0930

Gnomad AFR exome AF: 0.114

Gnomad AMR exome AF: 0.141

Gnomad ASJ exome AF: 0.113

Gnomad EAS exome AF: 0.122

Gnomad FIN exome AF: 0.0612

Gnomad NFE exome AF: 0.0742

Gnomad OTH exome AF: 0.119

GnomAD4 exome AF: 0.105 AC: 34291 AN: 325108 Hom.: 3 Cov.: 0 AF XY: 0.105 AC XY: 18635 AN XY: 178044

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

African (AFR) AF: 0.139 AC: 1160 AN: 8340

American (AMR) AF: 0.102 AC: 1553 AN: 15248

Ashkenazi Jewish (ASJ) AF: 0.0948 AC: 810 AN: 8548

East Asian (EAS) AF: 0.108 AC: 1730 AN: 16024

South Asian (SAS) AF: 0.106 AC: 4229 AN: 39800

European-Finnish (FIN) AF: 0.0873 AC: 1789 AN: 20492

Middle Eastern (MID) AF: 0.117 AC: 128 AN: 1090

European-Non Finnish (NFE) AF: 0.106 AC: 21162 AN: 199778

Other (OTH) AF: 0.110 AC: 1730 AN: 15788

⚠️ 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: 0.0317 AC: 3450 AN: 108904 Hom.: 26 Cov.: 0 AF XY: 0.0320 AC XY: 1583 AN XY: 49430

African (AFR) AF: 0.0396 AC: 1142 AN: 28858

American (AMR) AF: 0.0327 AC: 264 AN: 8070

Ashkenazi Jewish (ASJ) AF: 0.0223 AC: 68 AN: 3046

East Asian (EAS) AF: 0.0251 AC: 94 AN: 3742

South Asian (SAS) AF: 0.0688 AC: 224 AN: 3258

European-Finnish (FIN) AF: 0.0406 AC: 92 AN: 2266

Middle Eastern (MID) AF: 0.0267 AC: 4 AN: 150

European-Non Finnish (NFE) AF: 0.0266 AC: 1524 AN: 57244

Other (OTH) AF: 0.0266 AC: 38 AN: 1428

Alfa AF: 0.0139 Hom.: 909

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.30
Mutation Taster		=100/0	polymorphism

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: rs370261571; hg19: chr5-70757785;