chr5-71461958-C-CTTT

Position:

• chr5-71461958-C-CTTT

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_Moderate BS1 BS2

The NM_018429.3(BDP1):​c.599+51_599+53dup 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 0.0053 (7 hom., cov: 0)
  • Exomes 𝑓: 0.015 (2 hom.)
• Consequence: BDP1 NM_018429.3 intron
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.304

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]

ACMG classification

Verdict is Benign. Variant got -10 ACMG points.

• BP6: Variant 5-71461958-C-CTTT is Benign according to our data. Variant chr5-71461958-C-CTTT is described in ClinVar as [Likely_benign]. Clinvar id is 1317949.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population mid. gnomad4_exome allele frequency = 0.0151 (4974/330288) while in subpopulation MID AF= 0.0217 (24/1106). AF 95% confidence interval is 0.0186. There are 2 homozygotes in gnomad4_exome. There are 2684 alleles in male gnomad4_exome subpopulation. Median coverage is 0. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd4 at 7 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
BDP1	NM_018429.3	c.599+51_599+53dup		intron_variant		ENST00000358731.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
BDP1	ENST00000358731.9	c.599+51_599+53dup		intron_variant		1	NM_018429.3	P1
BDP1	ENST00000508917.6	n.791+51_791+53dup		intron_variant, non_coding_transcript_variant		1

Frequencies

GnomAD3 genomes AF: 0.00532 AC: 579 AN: 108936 Hom.: 7 Cov.: 0

Gnomad AFR AF: 0.00267

Gnomad AMI AF: 0.0119

Gnomad AMR AF: 0.00346

Gnomad ASJ AF: 0.00855

Gnomad EAS AF: 0.00826

Gnomad SAS AF: 0.00395

Gnomad FIN AF: 0.00440

Gnomad MID AF: 0.00610

Gnomad NFE AF: 0.00657

Gnomad OTH AF: 0.00492

GnomAD3 exomes AF: 0.0162 AC: 762 AN: 47180 Hom.: 9 AF XY: 0.0167 AC XY: 413 AN XY: 24802

Gnomad AFR exome AF: 0.0170

Gnomad AMR exome AF: 0.0247

Gnomad ASJ exome AF: 0.0132

Gnomad EAS exome AF: 0.0203

Gnomad SAS exome AF: 0.0194

Gnomad FIN exome AF: 0.00284

Gnomad NFE exome AF: 0.0133

Gnomad OTH exome AF: 0.0207

GnomAD4 exome AF: 0.0151 AC: 4974 AN: 330288 Hom.: 2 Cov.: 0 AF XY: 0.0148 AC XY: 2684 AN XY: 181036

Gnomad4 AFR exome AF: 0.0138

Gnomad4 AMR exome AF: 0.0200

Gnomad4 ASJ exome AF: 0.0163

Gnomad4 EAS exome AF: 0.0140

Gnomad4 SAS exome AF: 0.0197

Gnomad4 FIN exome AF: 0.00961

Gnomad4 NFE exome AF: 0.0145

Gnomad4 OTH exome AF: 0.0136

GnomAD4 genome AF: 0.00533 AC: 580 AN: 108920 Hom.: 7 Cov.: 0 AF XY: 0.00506 AC XY: 250 AN XY: 49452

Gnomad4 AFR AF: 0.00270

Gnomad4 AMR AF: 0.00346

Gnomad4 ASJ AF: 0.00855

Gnomad4 EAS AF: 0.00830

Gnomad4 SAS AF: 0.00398

Gnomad4 FIN AF: 0.00440

Gnomad4 NFE AF: 0.00657

Gnomad4 OTH AF: 0.00490

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

GeneDx

Sep 27, 2019

- -

Computational scores

Source: dbNSFP v4.3

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs370261571; hg19: chr5-70757785;