4-13576948-A-C

Variant names:

• chr4-13576948-A-C
• rs191479552
• NM_148894.3:c.8928T>G

Variant summary

Our verdict is Likely benign. The variant received -6 ACMG points: 0P and 6B. BP4_Strong BP6_Moderate

The NM_148894.3(BOD1L1):​c.8928T>G​(p.Asp2976Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000273 in 1,613,934 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.000046 (0 hom., cov: 33)
  • Exomes 𝑓: 0.000025 (1 hom.)
• Consequence: BOD1L1 NM_148894.3 missense
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.253

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

Our verdict: Likely_benign. The variant received -6 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.009590924).
• BP6: Variant 4-13576948-A-C is Benign according to our data. Variant chr4-13576948-A-C is described in ClinVar as [Likely_benign]. Clinvar id is 3134751.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
BOD1L1	NM_148894.3	c.8928T>G	p.Asp2976Glu	missense_variant	Exon 25 of 26	ENST00000040738.10	NP_683692.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
BOD1L1	ENST00000040738.10	c.8928T>G	p.Asp2976Glu	missense_variant	Exon 25 of 26	1	NM_148894.3	ENSP00000040738.5
BOD1L1	ENST00000507943.2	c.8928T>G	p.Asp2976Glu	missense_variant	Exon 25 of 27	3		ENSP00000425492.2
BOD1L1	ENST00000505343.1	n.749T>G		non_coding_transcript_exon_variant	Exon 3 of 4	3

Frequencies

GnomAD3 genomes AF: 0.0000460 AC: 7 AN: 152136 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000772

Gnomad SAS AF: 0.000414

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.000479

GnomAD2 exomes AF: 0.0000644 AC: 16 AN: 248370 AF XY: 0.0000670

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.000816

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000253 AC: 37 AN: 1461680 Hom.: 1 Cov.: 32 AF XY: 0.0000275 AC XY: 20 AN XY: 727112

African (AFR) AF: 0.00 AC: 0 AN: 33478

American (AMR) AF: 0.00 AC: 0 AN: 44720

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26136

East Asian (EAS) AF: 0.000479 AC: 19 AN: 39700

South Asian (SAS) AF: 0.000185 AC: 16 AN: 86256

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53402

Middle Eastern (MID) AF: 0.000173 AC: 1 AN: 5768

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1111848

Other (OTH) AF: 0.0000166 AC: 1 AN: 60372

GnomAD4 genome AF: 0.0000460 AC: 7 AN: 152254 Hom.: 0 Cov.: 33 AF XY: 0.0000672 AC XY: 5 AN XY: 74438

African (AFR) AF: 0.00 AC: 0 AN: 41548

American (AMR) AF: 0.00 AC: 0 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.000774 AC: 4 AN: 5168

South Asian (SAS) AF: 0.000414 AC: 2 AN: 4826

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10610

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 68020

Other (OTH) AF: 0.000474 AC: 1 AN: 2110

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.000102

ExAC AF: 0.0000659 AC: 8

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Benign:1

Sep 22, 2023

Ambry Genetics

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.090
BayesDel_addAF	Benign	-0.65	T
BayesDel_noAF	Benign	-0.77
CADD	Benign	0.20
DANN	Benign	0.18
DEOGEN2	Benign	0.0072	T
Eigen	Benign	-1.0
Eigen_PC	Benign	-1.0
FATHMM_MKL	Benign	0.073	N
LIST_S2	Benign	0.46	T
M_CAP	Benign	0.0017	T
MetaRNN	Benign	0.0096	T
MetaSVM	Benign	-0.99	T
MutationAssessor	Benign	-2.1	N
PhyloP100		-0.25
PrimateAI	Benign	0.41	T
PROVEAN	Benign	0.92	N
REVEL	Benign	0.033
Sift	Benign	1.0	T
Sift4G	Benign	1.0	T
Polyphen		0.0	B
Vest4		0.097
MutPred		0.096		Loss of helix (P = 0.0558);
MVP		0.043
MPC		0.044
ClinPred		0.015	T
GERP RS		-1.7
Varity_R		0.017
gMVP		0.011
Mutation Taster		=95/5	polymorphism

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

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Other links and lift over

dbSNP: rs191479552; hg19: chr4-13578572;