chr5-71461958-C-CT

Variant names:

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

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

• Frequency:
  • Genomes: 𝑓 0.65 (25661 hom., cov: 0)
  • Exomes 𝑓: 0.26 (161 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: 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-CT is Benign according to our data. Variant chr5-71461958-C-CT is described in ClinVar as Benign. ClinVar VariationId is 1250600.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.798 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+53dupT		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+33insT		intron	N/A	ENSP00000351575.4	A6H8Y1-1
	BDP1	ENST00000508917.6	TSL:1	n.791+32_791+33insT		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.651 AC: 71137 AN: 109244 Hom.: 25684 Cov.: 0

Gnomad AFR AF: 0.353

Gnomad AMI AF: 0.803

Gnomad AMR AF: 0.727

Gnomad ASJ AF: 0.793

Gnomad EAS AF: 0.822

Gnomad SAS AF: 0.739

Gnomad FIN AF: 0.642

Gnomad MID AF: 0.675

Gnomad NFE AF: 0.763

Gnomad OTH AF: 0.709

GnomAD2 exomes AF: 0.177 AC: 8333 AN: 47180 AF XY: 0.165

Gnomad AFR exome AF: 0.137

Gnomad AMR exome AF: 0.275

Gnomad ASJ exome AF: 0.237

Gnomad EAS exome AF: 0.259

Gnomad FIN exome AF: 0.0726

Gnomad NFE exome AF: 0.140

Gnomad OTH exome AF: 0.228

GnomAD4 exome AF: 0.261 AC: 85510 AN: 327906 Hom.: 161 Cov.: 0 AF XY: 0.259 AC XY: 46529 AN XY: 179750

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

African (AFR) AF: 0.171 AC: 1425 AN: 8326

American (AMR) AF: 0.245 AC: 3778 AN: 15428

Ashkenazi Jewish (ASJ) AF: 0.261 AC: 2247 AN: 8594

East Asian (EAS) AF: 0.290 AC: 4696 AN: 16186

South Asian (SAS) AF: 0.246 AC: 9910 AN: 40238

European-Finnish (FIN) AF: 0.204 AC: 4219 AN: 20666

Middle Eastern (MID) AF: 0.250 AC: 277 AN: 1108

European-Non Finnish (NFE) AF: 0.272 AC: 54725 AN: 201462

Other (OTH) AF: 0.266 AC: 4233 AN: 15898

⚠️ 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: 0.651 AC: 71092 AN: 109228 Hom.: 25661 Cov.: 0 AF XY: 0.645 AC XY: 31995 AN XY: 49594

African (AFR) AF: 0.353 AC: 10206 AN: 28918

American (AMR) AF: 0.727 AC: 5884 AN: 8098

Ashkenazi Jewish (ASJ) AF: 0.793 AC: 2423 AN: 3054

East Asian (EAS) AF: 0.822 AC: 3074 AN: 3740

South Asian (SAS) AF: 0.741 AC: 2424 AN: 3272

European-Finnish (FIN) AF: 0.642 AC: 1461 AN: 2274

Middle Eastern (MID) AF: 0.658 AC: 100 AN: 152

European-Non Finnish (NFE) AF: 0.763 AC: 43832 AN: 57446

Other (OTH) AF: 0.707 AC: 1012 AN: 1432

Alfa AF: 0.415 Hom.: 909

ClinVar

ClinVar submissions

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

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: rs370261571; hg19: chr5-70757785;