Variant 4-13587725-T-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_148894.3(BOD1L1):c.8327A>T(p.His2776Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000213 in 1,407,810 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.000021 ( 0 hom. )

Consequence

BOD1L1
NM_148894.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.00

Variant links:

Genes affected

BOD1L1 (HGNC:31792): (biorientation of chromosomes in cell division 1 like 1) Predicted to enable protein phosphatase 2A binding activity and protein phosphatase inhibitor activity. Involved in cellular response to DNA damage stimulus and replication fork processing. Located in nucleoplasm. [provided by Alliance of Genome Resources, Apr 2022]

BOD1L1 links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.106438965).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
BOD1L1	NM_148894.3 linkuse as main transcript	c.8327A>T	p.His2776Leu	missense_variant	16/26	ENST00000040738.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris
BOD1L1	ENST00000040738.10 linkuse as main transcript	c.8327A>T	p.His2776Leu	missense_variant	16/26	1	NM_148894.3	P2
BOD1L1	ENST00000507943.2 linkuse as main transcript	c.8327A>T	p.His2776Leu	missense_variant	16/27	3		A2
BOD1L1	ENST00000511119.1 linkuse as main transcript	n.1777A>T		non_coding_transcript_exon_variant	4/7	4

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.0000169

AC:

AN:

177110

Hom.:

AF XY:

0.0000107

AC XY:

AN XY:

93036

show subpopulations

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:

0.00

Gnomad NFE exome

AF:

0.0000421

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000213

AC:

AN:

1407810

Hom.:

Cov.:

AF XY:

0.0000201

AC XY:

AN XY:

695432

show subpopulations

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:

0.00

Gnomad4 NFE exome

AF:

0.0000259

Gnomad4 OTH exome

AF:

0.0000343

GnomAD4 genome

Cov.:

Alfa

AF:

0.0000282

Hom.:

Bravo

AF:

0.0000113

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jan 11, 2023

The c.8327A>T (p.H2776L) alteration is located in exon 16 (coding exon 16) of the BOD1L1 gene. This alteration results from a A to T substitution at nucleotide position 8327, causing the histidine (H) at amino acid position 2776 to be replaced by a leucine (L). 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

0.11

BayesDel_addAF

Benign

-0.20

BayesDel_noAF

Benign

-0.53

Cadd

Benign

Dann

Benign

0.94

DEOGEN2

Benign

0.047

Eigen

Benign

-0.15

Eigen_PC

Benign

-0.015

FATHMM_MKL

Benign

0.56

LIST_S2

Benign

0.64

M_CAP

Benign

0.0091

MetaRNN

Benign

0.11

MetaSVM

Benign

-1.0

MutationAssessor

Uncertain

2.3

MutationTaster

Benign

1.0

PrimateAI

Benign

0.38

PROVEAN

Uncertain

-2.8

REVEL

Benign

0.045

Sift

Uncertain

0.0030

Sift4G

Benign

0.61

Polyphen

0.24

Vest4

0.27

MutPred

0.25

Gain of sheet (P = 0.0344);

MVP

0.11

MPC

0.054

ClinPred

0.76

GERP RS

5.0

Varity_R

0.12

gMVP

0.17

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