5-71510822-T-G

Variant names:

• chr5-71510822-T-G
• rs1961760
• NM_018429.3:c.3730T>G

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_018429.3(BDP1):​c.3730T>G​(p.Phe1244Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. F1244I) has been classified as Benign.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: BDP1 NM_018429.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0710

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 -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.03520882).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
BDP1	NM_018429.3	c.3730T>G	p.Phe1244Val	missense_variant	Exon 17 of 39	ENST00000358731.9	NP_060899.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
BDP1	ENST00000358731.9	c.3730T>G	p.Phe1244Val	missense_variant	Exon 17 of 39	1	NM_018429.3	ENSP00000351575.4
BDP1	ENST00000508917.6	n.3922T>G		non_coding_transcript_exon_variant	Exon 17 of 32	1
BDP1	ENST00000508157.3	n.2875T>G		non_coding_transcript_exon_variant	Exon 6 of 6	5

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD3 exomes AF: 0.00000403 AC: 1 AN: 248262 Hom.: 0 AF XY: 0.00 AC XY: 0 AN XY: 134814

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.0000464

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 6.84e-7 AC: 1 AN: 1461202 Hom.: 0 Cov.: 52 AF XY: 0.00 AC XY: 0 AN XY: 726982

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.0000187

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

ExAC AF: 0.00000828 AC: 1

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.062
BayesDel_addAF	Benign	-0.43	T
BayesDel_noAF	Benign	-0.86
CADD	Benign	0.37
DANN	Benign	0.51
DEOGEN2	Benign	0.0032	T
Eigen	Benign	-1.7
Eigen_PC	Benign	-1.7
FATHMM_MKL	Benign	0.0020	N
LIST_S2	Benign	0.13	T
M_CAP	Benign	0.0020	T
MetaRNN	Benign	0.035	T
MetaSVM	Benign	-0.99	T
MutationAssessor	Benign	-0.69	N
PrimateAI	Benign	0.30	T
PROVEAN	Benign	0.95	N
REVEL	Benign	0.0030
Sift	Benign	0.46	T
Sift4G	Benign	0.42	T
Polyphen		0.0	B
Vest4		0.040
MutPred		0.29		Gain of MoRF binding (P = 0.1743);
MVP		0.040
MPC		0.044
ClinPred		0.043	T
GERP RS		-4.5
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.025
gMVP		0.026

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: rs1961760; hg19: chr5-70806649;