Genetic Variant CENPBD1P:n.184G>A (chr16-89971739-C-T) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NR_172519.1(CENPBD1P):n.758G>A variant causes a non coding transcript exon change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000255 in 1,611,984 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00048 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00023 ( 0 hom. )

Consequence

CENPBD1P
NR_172519.1 non_coding_transcript_exon

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.551

Variant links:

Genes affected

CENPBD1P (HGNC:28272): (CENPB DNA-binding domain containing 1, pseudogene) Predicted to enable DNA binding activity. Predicted to be located in nucleus. [provided by Alliance of Genome Resources, Apr 2022]

CENPBD1P links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

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=0.0053396523).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CENPBD1P	NR_172519.1 link	n.758G>A		non_coding_transcript_exon_variant	Exon 1 of 1

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL
CENPBD1P	ENST00000565150.2 link	n.184G>A	non_coding_transcript_exon_variant	Exon 1 of 1	5
CENPBD1P	ENST00000646748.1 link	n.796G>A	non_coding_transcript_exon_variant	Exon 1 of 1
CENPBD1P	ENST00000567035.1 link	n.257+190G>A	intron_variant	Intron 1 of 1	3

Frequencies

GnomAD3 genomes

AF:

0.000481

AC:

AN:

151812

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000484

Gnomad AMI

AF:

0.0471

Gnomad AMR

AF:

0.0000657

Gnomad ASJ

AF:

0.00202

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.000189

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000265

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000284

AC:

AN:

246830

Hom.:

AF XY:

0.000299

AC XY:

AN XY:

133904

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00334

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000166

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000285

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.000231

AC:

338

AN:

1460172

Hom.:

Cov.:

AF XY:

0.000237

AC XY:

172

AN XY:

726170

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00281

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000233

Gnomad4 FIN exome

AF:

0.0000189

Gnomad4 NFE exome

AF:

0.000204

Gnomad4 OTH exome

AF:

0.000282

GnomAD4 genome

AF:

0.000481

AC:

AN:

151812

Hom.:

Cov.:

AF XY:

0.000486

AC XY:

AN XY:

74104

show subpopulations

Gnomad4 AFR

AF:

0.0000484

Gnomad4 AMR

AF:

0.0000657

Gnomad4 ASJ

AF:

0.00202

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.000189

Gnomad4 NFE

AF:

0.000265

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000554

Hom.:

Bravo

AF:

0.000672

ESP6500AA

AF:

0.000241

AC:

ESP6500EA

AF:

0.000472

AC:

ExAC

AF:

0.000248

AC:

EpiCase

AF:

0.000436

EpiControl

AF:

0.000178

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Jan 04, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.184G>A (p.E62K) alteration is located in exon 1 (coding exon 1) of the CENPBD1 gene. This alteration results from a G to A substitution at nucleotide position 184, causing the glutamic acid (E) at amino acid position 62 to be replaced by a lysine (K). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.14

BayesDel_addAF

Benign

-0.42

BayesDel_noAF

Benign

-0.48

CADD

Benign

6.8

DANN

Uncertain

0.98

DEOGEN2

Benign

0.0086

Eigen

Benign

-0.49

Eigen_PC

Benign

-0.61

FATHMM_MKL

Benign

0.068

LIST_S2

Benign

0.69

M_CAP

Benign

0.0066

MetaRNN

Benign

0.0053

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.1

PrimateAI

Benign

0.44

PROVEAN

Benign

-1.9

REVEL

Benign

0.11

Sift

Benign

0.34

Sift4G

Benign

0.062

Polyphen

0.86

Vest4

0.17

MVP

0.33

MPC

0.062

ClinPred

0.042

GERP RS

3.2

Varity_R

0.15

gMVP

0.23

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over