rs279290

Variant names:

• chr5-71544606-A-G
• rs279290
• NM_018429.3:c.6563+99A>G

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_018429.3(BDP1):​c.6563+99A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.485 in 1,329,880 control chromosomes in the GnomAD database, including 156,261 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.46 (16664 hom., cov: 32)
  • Exomes 𝑓: 0.49 (139597 hom.)
• Consequence: BDP1 NM_018429.3 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -2.32
• Publications: 7 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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.03).
• BP6: Variant 5-71544606-A-G is Benign according to our data. Variant chr5-71544606-A-G is described in ClinVar as Benign. ClinVar VariationId is 1228769.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.53 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
BDP1	NM_018429.3	c.6563+99A>G		intron_variant	Intron 31 of 38	ENST00000358731.9	NP_060899.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
BDP1	ENST00000358731.9	c.6563+99A>G		intron_variant	Intron 31 of 38	1	NM_018429.3	ENSP00000351575.4
BDP1	ENST00000508917.6	n.6755+99A>G		intron_variant	Intron 31 of 31	1
BDP1	ENST00000525844.1	n.629+99A>G		intron_variant	Intron 5 of 13	1		ENSP00000432404.1
BDP1	ENST00000514903.7	n.1328+99A>G		intron_variant	Intron 8 of 15	5		ENSP00000421910.3

Frequencies

GnomAD3 genomes AF: 0.464 AC: 70509 AN: 151846 Hom.: 16654 Cov.: 32

Gnomad AFR AF: 0.445

Gnomad AMI AF: 0.643

Gnomad AMR AF: 0.365

Gnomad ASJ AF: 0.475

Gnomad EAS AF: 0.369

Gnomad SAS AF: 0.548

Gnomad FIN AF: 0.531

Gnomad MID AF: 0.449

Gnomad NFE AF: 0.486

Gnomad OTH AF: 0.459

GnomAD4 exome AF: 0.487 AC: 573893 AN: 1177916 Hom.: 139597 AF XY: 0.489 AC XY: 287142 AN XY: 587170

African (AFR) AF: 0.449 AC: 11673 AN: 25978

American (AMR) AF: 0.307 AC: 8386 AN: 27360

Ashkenazi Jewish (ASJ) AF: 0.487 AC: 9373 AN: 19240

East Asian (EAS) AF: 0.371 AC: 13601 AN: 36650

South Asian (SAS) AF: 0.549 AC: 34025 AN: 61972

European-Finnish (FIN) AF: 0.526 AC: 25190 AN: 47904

Middle Eastern (MID) AF: 0.500 AC: 2297 AN: 4592

European-Non Finnish (NFE) AF: 0.492 AC: 445283 AN: 904338

Other (OTH) AF: 0.482 AC: 24065 AN: 49882

GnomAD4 genome AF: 0.464 AC: 70554 AN: 151964 Hom.: 16664 Cov.: 32 AF XY: 0.465 AC XY: 34564 AN XY: 74252

African (AFR) AF: 0.446 AC: 18475 AN: 41466

American (AMR) AF: 0.364 AC: 5562 AN: 15266

Ashkenazi Jewish (ASJ) AF: 0.475 AC: 1650 AN: 3472

East Asian (EAS) AF: 0.369 AC: 1898 AN: 5146

South Asian (SAS) AF: 0.548 AC: 2643 AN: 4824

European-Finnish (FIN) AF: 0.531 AC: 5594 AN: 10528

Middle Eastern (MID) AF: 0.446 AC: 131 AN: 294

European-Non Finnish (NFE) AF: 0.486 AC: 33050 AN: 67948

Other (OTH) AF: 0.458 AC: 967 AN: 2112

Alfa AF: 0.466 Hom.: 2152

Bravo AF: 0.445

Asia WGS AF: 0.452 AC: 1572 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Jun 24, 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	-1.0
CADD	Benign	0.92
DANN	Benign	0.42
PhyloP100		-2.3
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: rs279290; hg19: chr5-70840433;