5-71461958-C-CTT

Variant names:

• chr5-71461958-C-CTT
• rs370261571
• NM_018429.3:c.599+52_599+53dupTT

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+52_599+53dupTT variant causes a intron change involving the alteration of a non-conserved nucleotide. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.037 (151 hom., cov: 0)
  • Exomes 𝑓: 0.084 (6 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-C-CTT is Benign according to our data. Variant chr5-71461958-C-CTT is described in ClinVar as Benign. ClinVar VariationId is 1294001.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0506 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+52_599+53dupTT		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+33insTT		intron	N/A	ENSP00000351575.4	A6H8Y1-1
	BDP1	ENST00000508917.6	TSL:1	n.791+32_791+33insTT		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.0374 AC: 4071 AN: 108832 Hom.: 151 Cov.: 0

Gnomad AFR AF: 0.0528

Gnomad AMI AF: 0.0251

Gnomad AMR AF: 0.0439

Gnomad ASJ AF: 0.0529

Gnomad EAS AF: 0.0261

Gnomad SAS AF: 0.0268

Gnomad FIN AF: 0.0101

Gnomad MID AF: 0.0671

Gnomad NFE AF: 0.0307

Gnomad OTH AF: 0.0289

GnomAD2 exomes AF: 0.0679 AC: 3205 AN: 47180 AF XY: 0.0645

Gnomad AFR exome AF: 0.0566

Gnomad AMR exome AF: 0.108

Gnomad ASJ exome AF: 0.0805

Gnomad EAS exome AF: 0.0953

Gnomad FIN exome AF: 0.0207

Gnomad NFE exome AF: 0.0543

Gnomad OTH exome AF: 0.0850

GnomAD4 exome AF: 0.0838 AC: 27005 AN: 322170 Hom.: 6 Cov.: 0 AF XY: 0.0838 AC XY: 14792 AN XY: 176416

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

African (AFR) AF: 0.0625 AC: 514 AN: 8220

American (AMR) AF: 0.0966 AC: 1464 AN: 15148

Ashkenazi Jewish (ASJ) AF: 0.0926 AC: 788 AN: 8512

East Asian (EAS) AF: 0.0834 AC: 1329 AN: 15932

South Asian (SAS) AF: 0.0994 AC: 3883 AN: 39060

European-Finnish (FIN) AF: 0.0599 AC: 1223 AN: 20424

Middle Eastern (MID) AF: 0.0972 AC: 105 AN: 1080

European-Non Finnish (NFE) AF: 0.0825 AC: 16341 AN: 198134

Other (OTH) AF: 0.0867 AC: 1358 AN: 15660

⚠️ 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: 0.0374 AC: 4069 AN: 108816 Hom.: 151 Cov.: 0 AF XY: 0.0370 AC XY: 1828 AN XY: 49402

African (AFR) AF: 0.0528 AC: 1523 AN: 28866

American (AMR) AF: 0.0437 AC: 352 AN: 8050

Ashkenazi Jewish (ASJ) AF: 0.0529 AC: 161 AN: 3046

East Asian (EAS) AF: 0.0263 AC: 98 AN: 3732

South Asian (SAS) AF: 0.0267 AC: 87 AN: 3260

European-Finnish (FIN) AF: 0.0101 AC: 23 AN: 2272

Middle Eastern (MID) AF: 0.0667 AC: 10 AN: 150

European-Non Finnish (NFE) AF: 0.0307 AC: 1754 AN: 57180

Other (OTH) AF: 0.0281 AC: 40 AN: 1424

Alfa AF: 0.0143 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 (auto)

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;