5-71461958-CTTTTTTTTTTTTT-CTTTTTTTTTTTTTTTTTT

Variant names:

• chr5-71461958-C-CTTTTT
• rs370261571
• NM_018429.3:c.599+49_599+53dupTTTTT

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+49_599+53dupTTTTT 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 0.0040 (5 hom., cov: 0)
  • Exomes 𝑓: 0.00060 (0 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-CTTTTT is Benign according to our data. Variant chr5-71461958-C-CTTTTT is described in ClinVar as Likely_benign. ClinVar VariationId is 1700524.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High Homozygotes in GnomAd4 at 5 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+49_599+53dupTTTTT		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+33insTTTTT		intron	N/A	ENSP00000351575.4	A6H8Y1-1
	BDP1	ENST00000508917.6	TSL:1	n.791+32_791+33insTTTTT		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.00404 AC: 441 AN: 109052 Hom.: 5 Cov.: 0

Gnomad AFR AF: 0.0145

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00124

Gnomad ASJ AF: 0.000328

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000157

Gnomad OTH AF: 0.00211

GnomAD4 exome AF: 0.000603 AC: 202 AN: 334714 Hom.: 0 Cov.: 0 AF XY: 0.000621 AC XY: 114 AN XY: 183564

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

African (AFR) AF: 0.00353 AC: 30 AN: 8490

American (AMR) AF: 0.000446 AC: 7 AN: 15712

Ashkenazi Jewish (ASJ) AF: 0.000801 AC: 7 AN: 8744

East Asian (EAS) AF: 0.000425 AC: 7 AN: 16466

South Asian (SAS) AF: 0.00101 AC: 42 AN: 41608

European-Finnish (FIN) AF: 0.0000954 AC: 2 AN: 20968

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 1120

European-Non Finnish (NFE) AF: 0.000448 AC: 92 AN: 205340

Other (OTH) AF: 0.000922 AC: 15 AN: 16266

⚠️ 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: 0.00404 AC: 441 AN: 109036 Hom.: 5 Cov.: 0 AF XY: 0.00426 AC XY: 211 AN XY: 49500

African (AFR) AF: 0.0145 AC: 418 AN: 28884

American (AMR) AF: 0.00124 AC: 10 AN: 8082

Ashkenazi Jewish (ASJ) AF: 0.000328 AC: 1 AN: 3050

East Asian (EAS) AF: 0.00 AC: 0 AN: 3740

South Asian (SAS) AF: 0.00 AC: 0 AN: 3268

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 2272

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 150

European-Non Finnish (NFE) AF: 0.000157 AC: 9 AN: 57320

Other (OTH) AF: 0.00210 AC: 3 AN: 1428

Alfa AF: 0.00 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;