5-71461958-CTTTTTTTTTTTTT-CTTTTTTTTTTTTTTTT

Variant names:

• chr5-71461958-C-CTTT
• rs370261571
• NM_018429.3:c.599+51_599+53dupTTT

Variant summary

Our verdict is Likely benign. The variant received -6 ACMG points: 0P and 6B. BP6_Moderate BS2

The NM_018429.3(BDP1):​c.599+51_599+53dupTTT variant causes a intron change involving the alteration of a non-conserved nucleotide. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0053 (7 hom., cov: 0)
  • Exomes 𝑓: 0.015 (2 hom.)
• Consequence: BDP1 NM_018429.3 intron
• Clinical Significance: Likely 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: Ambry Genetics
• nonsyndromic genetic hearing loss

  Inheritance: AR Classification: LIMITED Submitted by: ClinGen

ACMG classification

Our verdict: Likely_benign. The variant received -6 ACMG points.

• BP6: Variant 5-71461958-C-CTTT is Benign according to our data. Variant chr5-71461958-C-CTTT is described in ClinVar as Likely_benign. ClinVar VariationId is 1317949.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High Homozygotes in GnomAd4 at 7 AR gene

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+51_599+53dupTTT		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+33insTTT		intron	N/A	ENSP00000351575.4	A6H8Y1-1
	BDP1	ENST00000508917.6	TSL:1	n.791+32_791+33insTTT		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.00532 AC: 579 AN: 108936 Hom.: 7 Cov.: 0

Gnomad AFR AF: 0.00267

Gnomad AMI AF: 0.0119

Gnomad AMR AF: 0.00346

Gnomad ASJ AF: 0.00855

Gnomad EAS AF: 0.00826

Gnomad SAS AF: 0.00395

Gnomad FIN AF: 0.00440

Gnomad MID AF: 0.00610

Gnomad NFE AF: 0.00657

Gnomad OTH AF: 0.00492

GnomAD2 exomes AF: 0.0162 AC: 762 AN: 47180 AF XY: 0.0167

Gnomad AFR exome AF: 0.0170

Gnomad AMR exome AF: 0.0247

Gnomad ASJ exome AF: 0.0132

Gnomad EAS exome AF: 0.0203

Gnomad FIN exome AF: 0.00284

Gnomad NFE exome AF: 0.0133

Gnomad OTH exome AF: 0.0207

GnomAD4 exome AF: 0.0151 AC: 4974 AN: 330288 Hom.: 2 Cov.: 0 AF XY: 0.0148 AC XY: 2684 AN XY: 181036

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

African (AFR) AF: 0.0138 AC: 116 AN: 8414

American (AMR) AF: 0.0200 AC: 310 AN: 15470

Ashkenazi Jewish (ASJ) AF: 0.0163 AC: 141 AN: 8648

East Asian (EAS) AF: 0.0140 AC: 228 AN: 16266

South Asian (SAS) AF: 0.0197 AC: 805 AN: 40816

European-Finnish (FIN) AF: 0.00961 AC: 200 AN: 20812

Middle Eastern (MID) AF: 0.0217 AC: 24 AN: 1106

European-Non Finnish (NFE) AF: 0.0145 AC: 2932 AN: 202690

Other (OTH) AF: 0.0136 AC: 218 AN: 16066

⚠️ 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: 0.00533 AC: 580 AN: 108920 Hom.: 7 Cov.: 0 AF XY: 0.00506 AC XY: 250 AN XY: 49452

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

African (AFR) AF: 0.00270 AC: 78 AN: 28886

American (AMR) AF: 0.00346 AC: 28 AN: 8084

Ashkenazi Jewish (ASJ) AF: 0.00855 AC: 26 AN: 3042

East Asian (EAS) AF: 0.00830 AC: 31 AN: 3736

South Asian (SAS) AF: 0.00398 AC: 13 AN: 3266

European-Finnish (FIN) AF: 0.00440 AC: 10 AN: 2272

Middle Eastern (MID) AF: 0.00667 AC: 1 AN: 150

European-Non Finnish (NFE) AF: 0.00657 AC: 376 AN: 57214

Other (OTH) AF: 0.00490 AC: 7 AN: 1428

⚠️ 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.

Alfa AF: 0.0275 Hom.: 909

ClinVar

ClinVar submissions

Significance: Likely 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

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

Other links and lift over

dbSNP: rs370261571; hg19: chr5-70757785;