5-71532590-TTTTGTTTG-TTTTG

Variant names:

• chr5-71532590-TTTTG-T
• rs2307799
• NM_018429.3:c.5892+173_5892+176delTTGT

Variant summary

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

The NM_018429.3(BDP1):​c.5892+173_5892+176delTTGT variant causes a intron change involving the alteration of a non-conserved nucleotide. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.30 (7825 hom., cov: 19)
• Consequence: BDP1 NM_018429.3 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.494
• Publications: 5 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: Benign. The variant received -10 ACMG points.

• BP6: Variant 5-71532590-TTTTG-T is Benign according to our data. Variant chr5-71532590-TTTTG-T is described in ClinVar as Benign. ClinVar VariationId is 1276613.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.484 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	BDP1	NM_018429.3	MANE Select	c.5892+173_5892+176delTTGT		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.5892+164_5892+167delTTTG		intron	N/A	ENSP00000351575.4
	BDP1	ENST00000508917.6	TSL:1	n.6084+164_6084+167delTTTG		intron	N/A
	BDP1	ENST00000525844.1	TSL:1	n.54+164_54+167delTTTG		intron	N/A	ENSP00000432404.1

Frequencies

GnomAD3 genomes AF: 0.300 AC: 45473 AN: 151774 Hom.: 7819 Cov.: 19

Gnomad AFR AF: 0.137

Gnomad AMI AF: 0.179

Gnomad AMR AF: 0.480

Gnomad ASJ AF: 0.411

Gnomad EAS AF: 0.500

Gnomad SAS AF: 0.290

Gnomad FIN AF: 0.274

Gnomad MID AF: 0.394

Gnomad NFE AF: 0.342

Gnomad OTH AF: 0.337

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

GnomAD4 genome AF: 0.299 AC: 45487 AN: 151894 Hom.: 7825 Cov.: 19 AF XY: 0.301 AC XY: 22341 AN XY: 74202

African (AFR) AF: 0.137 AC: 5665 AN: 41496

American (AMR) AF: 0.481 AC: 7320 AN: 15224

Ashkenazi Jewish (ASJ) AF: 0.411 AC: 1423 AN: 3460

East Asian (EAS) AF: 0.500 AC: 2569 AN: 5140

South Asian (SAS) AF: 0.291 AC: 1405 AN: 4826

European-Finnish (FIN) AF: 0.274 AC: 2886 AN: 10552

Middle Eastern (MID) AF: 0.394 AC: 115 AN: 292

European-Non Finnish (NFE) AF: 0.342 AC: 23234 AN: 67884

Other (OTH) AF: 0.335 AC: 707 AN: 2108

Alfa AF: 0.193 Hom.: 384

Bravo AF: 0.315

Asia WGS AF: 0.363 AC: 1257 AN: 3466

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Nov 10, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.49
Mutation Taster		=100/0	polymorphism (auto)

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: rs2307799; hg19: chr5-70828417; COSMIC: COSV104423776;