5-71552687-T-G

Position:

• chr5-71552687-T-G

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 2P and 8B. PM2 BP4_Strong BS1

The ENST00000358731.9(BDP1):​c.6996-429T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.011 in 125,770 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.011 (0 hom., cov: 34)
• Consequence: BDP1 ENST00000358731.9 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0650

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 Likely_benign. Variant got -6 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.96).
• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.011 (1388/125770) while in subpopulation AFR AF= 0.03 (896/29876). AF 95% confidence interval is 0.0284. There are 0 homozygotes in gnomad4. There are 695 alleles in male gnomad4 subpopulation. Median coverage is 34. This position pass quality control queck.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
BDP1	NM_018429.3	c.6996-429T>G		intron_variant		ENST00000358731.9	NP_060899.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
BDP1	ENST00000358731.9	c.6996-429T>G		intron_variant		1	NM_018429.3	ENSP00000351575	P1
BDP1	ENST00000525844.1	c.1062-429T>G		intron_variant, NMD_transcript_variant		1		ENSP00000432404
BDP1	ENST00000514903.7	c.1576-429T>G		intron_variant, NMD_transcript_variant		5		ENSP00000421910

Frequencies

GnomAD3 genomes AF: 0.0110 AC: 1384 AN: 125678 Hom.: 0 Cov.: 34

Gnomad AFR AF: 0.0300

Gnomad AMI AF: 0.00424

Gnomad AMR AF: 0.00701

Gnomad ASJ AF: 0.00292

Gnomad EAS AF: 0.0220

Gnomad SAS AF: 0.0126

Gnomad FIN AF: 0.00531

Gnomad MID AF: 0.00725

Gnomad NFE AF: 0.00302

Gnomad OTH AF: 0.00964

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

GnomAD4 genome AF: 0.0110 AC: 1388 AN: 125770 Hom.: 0 Cov.: 34 AF XY: 0.0113 AC XY: 695 AN XY: 61616

Gnomad4 AFR AF: 0.0300

Gnomad4 AMR AF: 0.00700

Gnomad4 ASJ AF: 0.00292

Gnomad4 EAS AF: 0.0220

Gnomad4 SAS AF: 0.0123

Gnomad4 FIN AF: 0.00531

Gnomad4 NFE AF: 0.00302

Gnomad4 OTH AF: 0.0107

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	4.9
DANN	Benign	0.36

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

Publications

LitVar

Other links and lift over

dbSNP: rs467880; hg19: chr5-70848514;