4-13581198-G-A

Position:

• chr4-13581198-G-A

Variant summary

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

The NM_148894.3(BOD1L1):​c.8602C>T​(p.Pro2868Ser) variant causes a missense change. The variant allele was found at a frequency of 0.00000212 in 1,412,466 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000021 (0 hom.)
• Consequence: BOD1L1 NM_148894.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.24

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 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
BOD1L1	NM_148894.3	c.8602C>T	p.Pro2868Ser	missense_variant	20/26	ENST00000040738.10	NP_683692.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
BOD1L1	ENST00000040738.10	c.8602C>T	p.Pro2868Ser	missense_variant	20/26	1	NM_148894.3	ENSP00000040738.5
BOD1L1	ENST00000507943.2	c.8602C>T	p.Pro2868Ser	missense_variant	20/27	3		ENSP00000425492.2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000212 AC: 3 AN: 1412466 Hom.: 0 Cov.: 31 AF XY: 0.00000143 AC XY: 1 AN XY: 698076

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.0000264

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: 0.00000184

Gnomad4 OTH exome AF: 0.00

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

Jul 01, 2024

The c.8602C>T (p.P2868S) alteration is located in exon 20 (coding exon 20) of the BOD1L1 gene. This alteration results from a C to T substitution at nucleotide position 8602, causing the proline (P) at amino acid position 2868 to be replaced by a serine (S). 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	Uncertain	0.42
BayesDel_addAF	Uncertain	0.049	T
BayesDel_noAF	Benign	-0.17
CADD	Pathogenic	27
DANN	Pathogenic	1.0
DEOGEN2	Benign	0.24	T
Eigen	Uncertain	0.63
Eigen_PC	Uncertain	0.64
FATHMM_MKL	Uncertain	0.96	D
LIST_S2	Benign	0.81	T
M_CAP	Benign	0.027	D
MetaRNN	Uncertain	0.70	D
MetaSVM	Benign	-1.0	T
MutationAssessor	Uncertain	2.6	M
PrimateAI	Benign	0.46	T
PROVEAN	Uncertain	-4.0	D
REVEL	Benign	0.23
Sift	Uncertain	0.0030	D
Sift4G	Benign	0.21	T
Polyphen		1.0	D
Vest4		0.63
MutPred		0.34		Gain of phosphorylation at P2868 (P = 0.0146);
MVP		0.28
MPC		0.32
ClinPred		0.94	D
GERP RS		5.5
Varity_R		0.31
gMVP		0.16

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: rs1303638793; hg19: chr4-13582822;