4-13587758-T-C

Variant summary

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

The NM_148894.3(BOD1L1):c.8294A>G(p.Glu2765Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000143 in 1,403,102 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: 0.0000014 (0 hom.)
• Consequence: BOD1L1 NM_148894.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.11

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=0.10997388).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
BOD1L1	NM_148894.3	c.8294A>G	p.Glu2765Gly	missense_variant	16/26	ENST00000040738.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
BOD1L1	ENST00000040738.10	c.8294A>G	p.Glu2765Gly	missense_variant	16/26	1	NM_148894.3	P2
BOD1L1	ENST00000507943.2	c.8294A>G	p.Glu2765Gly	missense_variant	16/27	3		A2
BOD1L1	ENST00000511119.1	n.1744A>G		non_coding_transcript_exon_variant	4/7	4

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000143 AC: 2 AN: 1403102 Hom.: 0 Cov.: 28 AF XY: 0.00000144 AC XY: 1 AN XY: 692894

Gnomad4 AFR exome AF: 0.0000623

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: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

Bravo AF: 0.00000378

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

Jul 26, 2022

The c.8294A>G (p.E2765G) alteration is located in exon 16 (coding exon 16) of the BOD1L1 gene. This alteration results from a A to G substitution at nucleotide position 8294, causing the glutamic acid (E) at amino acid position 2765 to be replaced by a glycine (G). 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	-0.18	T
BayesDel_noAF	Benign	-0.50
Cadd	Benign	23
Dann	Uncertain	0.99
DEOGEN2	Benign	0.031	T
Eigen	Benign	0.12
Eigen_PC	Benign	0.20
FATHMM_MKL	Benign	0.74	D
LIST_S2	Benign	0.72	T
M_CAP	Benign	0.0092	T
MetaRNN	Benign	0.11	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Uncertain	2.1	M
MutationTaster	Benign	0.78	D
PrimateAI	Benign	0.38	T
PROVEAN	Benign	-2.1	N
REVEL	Benign	0.032
Sift	Pathogenic	0.0	D
Sift4G	Uncertain	0.011	D
Polyphen		0.63	P
Vest4		0.21
MutPred		0.15		Gain of loop (P = 0.0079);
MVP		0.068
MPC		0.089
ClinPred		0.94	D
GERP RS		4.9
Varity_R		0.21
gMVP		0.26

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: rs1026387590; hg19: chr4-13589382;