4-13597127-G-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.7996C>G(p.Leu2666Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000132 in 1,442,408 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: 33)
  • Exomes 𝑓: 0.000013 (0 hom.)
• Consequence: BOD1L1 NM_148894.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.22

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=0.105231285).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
BOD1L1	NM_148894.3	c.7996C>G	p.Leu2666Val	missense_variant	11/26	ENST00000040738.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
BOD1L1	ENST00000040738.10	c.7996C>G	p.Leu2666Val	missense_variant	11/26	1	NM_148894.3	P2
BOD1L1	ENST00000507943.2	c.7996C>G	p.Leu2666Val	missense_variant	11/27	3		A2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD3 exomes AF: 0.00000897 AC: 2 AN: 223052 Hom.: 0 AF XY: 0.0000167 AC XY: 2 AN XY: 119492

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: 0.0000204

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000132 AC: 19 AN: 1442408 Hom.: 0 Cov.: 30 AF XY: 0.0000168 AC XY: 12 AN XY: 715472

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: 0.0000173

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

Dec 20, 2021

The c.7996C>G (p.L2666V) alteration is located in exon 11 (coding exon 11) of the BOD1L1 gene. This alteration results from a C to G substitution at nucleotide position 7996, causing the leucine (L) at amino acid position 2666 to be replaced by a valine (V). 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	-0.30	T
BayesDel_noAF	Benign	-0.64
Cadd	Benign	7.9
Dann	Benign	0.91
DEOGEN2	Benign	0.036	T
Eigen	Benign	-0.61
Eigen_PC	Benign	-0.68
FATHMM_MKL	Benign	0.18	N
LIST_S2	Benign	0.70	T
M_CAP	Benign	0.0084	T
MetaRNN	Benign	0.11	T
MetaSVM	Benign	-0.98	T
MutationAssessor	Benign	1.0	L
MutationTaster	Benign	1.0	N
PrimateAI	Benign	0.26	T
PROVEAN	Benign	-0.67	N
REVEL	Benign	0.031
Sift	Uncertain	0.013	D
Sift4G	Benign	0.44	T
Polyphen		0.76	P
Vest4		0.20
MutPred		0.24		Gain of sheet (P = 0.0344);
MVP		0.10
MPC		0.20
ClinPred		0.13	T
GERP RS		3.4
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.044
gMVP		0.12

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.040		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: rs1349990895; hg19: chr4-13598751;