4-13582705-G-T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_148894.3(BOD1L1):c.8465C>A(p.Pro2822His) 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. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: BOD1L1 NM_148894.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.88

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]

ACMG classification

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=0.07852742).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
BOD1L1	NM_148894.3	c.8465C>A	p.Pro2822His	missense_variant	18/26	ENST00000040738.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
BOD1L1	ENST00000040738.10	c.8465C>A	p.Pro2822His	missense_variant	18/26	1	NM_148894.3	P2
BOD1L1	ENST00000507943.2	c.8465C>A	p.Pro2822His	missense_variant	18/27	3		A2
BOD1L1	ENST00000511119.1	n.1915C>A		non_coding_transcript_exon_variant	6/7	4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 29

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Apr 13, 2022

The c.8465C>A (p.P2822H) alteration is located in exon 18 (coding exon 18) of the BOD1L1 gene. This alteration results from a C to A substitution at nucleotide position 8465, causing the proline (P) at amino acid position 2822 to be replaced by a histidine (H). 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	-0.25	T
BayesDel_noAF	Benign	-0.59
Cadd	Benign	18
Dann	Benign	0.96
DEOGEN2	Benign	0.013	T
Eigen	Benign	-0.61
Eigen_PC	Benign	-0.59
FATHMM_MKL	Benign	0.31	N
LIST_S2	Benign	0.55	T
M_CAP	Benign	0.014	T
MetaRNN	Benign	0.079	T
MetaSVM	Benign	-0.96	T
MutationAssessor	Benign	1.1	L
MutationTaster	Benign	1.0	N
PrimateAI	Benign	0.30	T
PROVEAN	Benign	-0.43	N
REVEL	Benign	0.055
Sift	Pathogenic	0.0	D
Sift4G	Uncertain	0.033	D
Polyphen		0.29	B
Vest4		0.23
MutPred		0.11		Loss of loop (P = 0.0022);
MVP		0.043
MPC		0.089
ClinPred		0.51	D
GERP RS		3.6
Varity_R		0.094
gMVP		0.086

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr4-13584329;