5-71552856-T-C

Variant names:

• chr5-71552856-T-C
• rs466930
• NM_018429.3:c.6996-260T>C

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_018429.3(BDP1):​c.6996-260T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.446 in 151,558 control chromosomes in the GnomAD database, including 15,405 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.45 (15405 hom., cov: 31)
• Consequence: BDP1 NM_018429.3 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.0480
• Publications: 2 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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BP6: Variant 5-71552856-T-C is Benign according to our data. Variant chr5-71552856-T-C is described in ClinVar as Benign. ClinVar VariationId is 1250427.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.531 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
BDP1	NM_018429.3	c.6996-260T>C		intron_variant	Intron 34 of 38	ENST00000358731.9	NP_060899.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
BDP1	ENST00000358731.9	c.6996-260T>C		intron_variant	Intron 34 of 38	1	NM_018429.3	ENSP00000351575.4
BDP1	ENST00000525844.1	n.1062-260T>C		intron_variant	Intron 8 of 13	1		ENSP00000432404.1
BDP1	ENST00000514903.7	n.1574-260T>C		intron_variant	Intron 10 of 15	5		ENSP00000421910.3

Frequencies

GnomAD3 genomes AF: 0.446 AC: 67514 AN: 151442 Hom.: 15404 Cov.: 31

Gnomad AFR AF: 0.379

Gnomad AMI AF: 0.644

Gnomad AMR AF: 0.357

Gnomad ASJ AF: 0.476

Gnomad EAS AF: 0.371

Gnomad SAS AF: 0.548

Gnomad FIN AF: 0.533

Gnomad MID AF: 0.443

Gnomad NFE AF: 0.487

Gnomad OTH AF: 0.449

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

GnomAD4 genome AF: 0.446 AC: 67541 AN: 151558 Hom.: 15405 Cov.: 31 AF XY: 0.448 AC XY: 33152 AN XY: 74058

African (AFR) AF: 0.379 AC: 15628 AN: 41274

American (AMR) AF: 0.357 AC: 5436 AN: 15232

Ashkenazi Jewish (ASJ) AF: 0.476 AC: 1650 AN: 3468

East Asian (EAS) AF: 0.371 AC: 1901 AN: 5126

South Asian (SAS) AF: 0.548 AC: 2638 AN: 4810

European-Finnish (FIN) AF: 0.533 AC: 5595 AN: 10498

Middle Eastern (MID) AF: 0.439 AC: 129 AN: 294

European-Non Finnish (NFE) AF: 0.487 AC: 33037 AN: 67842

Other (OTH) AF: 0.447 AC: 942 AN: 2106

Alfa AF: 0.444 Hom.: 1940

Bravo AF: 0.424

Asia WGS AF: 0.448 AC: 1559 AN: 3478

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 v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.70
DANN	Benign	0.20
PhyloP100		0.048
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: rs466930; hg19: chr5-70848683;