dbSNP rs12457997: BOD1P1:n.3415833C>T (chr18-3415833-C-T) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The variant allele was found at a frequency of 0.573 in 151,952 control chromosomes in the GnomAD database, including 26,908 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.57 ( 26908 hom., cov: 32)

Consequence

BOD1P1
intragenic

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.00

Publications

6 publications found

Variant links:

Genes affected

BOD1P1 (HGNC:51435): (biorientation of chromosomes in cell division 1 pseudogene 1)

BOD1P1 links:

TGIF1 (HGNC:11776): (TGFB induced factor homeobox 1) The protein encoded by this gene is a member of the three-amino acid loop extension (TALE) superclass of atypical homeodomains. TALE homeobox proteins are highly conserved transcription regulators. This particular homeodomain binds to a previously characterized retinoid X receptor responsive element from the cellular retinol-binding protein II promoter. In addition to its role in inhibiting 9-cis-retinoic acid-dependent RXR alpha transcription activation of the retinoic acid responsive element, the protein is an active transcriptional co-repressor of SMAD2 and may participate in the transmission of nuclear signals during development and in the adult. Mutations in this gene are associated with holoprosencephaly type 4, which is a structural anomaly of the brain. Alternative splicing has been observed at this locus and multiple splice variants encoding distinct isoforms are described. [provided by RefSeq, Jul 2013]

TGIF1 Gene-Disease associations (from GenCC):

holoprosencephaly 4
Inheritance: AD Classification: DEFINITIVE, STRONG, LIMITED Submitted by: Laboratory for Molecular Medicine, Labcorp Genetics (formerly Invitae), G2P, Ambry Genetics

TGIF1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.89).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.676 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	Protein
BOD1P1		n.3415833C>T	intragenic_variant
TGIF1	NM_001278686.3 link	c.-117-2310C>T	intron_variant	Intron 1 of 3	NP_001265615.1
TGIF1	NM_174886.3 link	c.-117-2310C>T	intron_variant	Intron 1 of 3	NP_777480.1

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	Protein
TGIF1	ENST00000401449.5 link	c.-117-2310C>T	intron_variant	Intron 1 of 3	2	ENSP00000385206.1
TGIF1	ENST00000548489.6 link	c.-117-2310C>T	intron_variant	Intron 1 of 3	3	ENSP00000447747.2
TGIF1	ENST00000552383.5 link	c.-117-2310C>T	intron_variant	Intron 1 of 3	2	ENSP00000449287.1

Frequencies

GnomAD3 genomes

AF:

0.573

AC:

86998

AN:

151834

Hom.:

26898

Cov.:

show subpopulations

Gnomad AFR

AF:

0.318

Gnomad AMI

AF:

0.605

Gnomad AMR

AF:

0.687

Gnomad ASJ

AF:

0.695

Gnomad EAS

AF:

0.693

Gnomad SAS

AF:

0.647

Gnomad FIN

AF:

0.672

Gnomad MID

AF:

0.646

Gnomad NFE

AF:

0.664

Gnomad OTH

AF:

0.605

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome

AF:

0.573

AC:

87022

AN:

151952

Hom.:

26908

Cov.:

AF XY:

0.577

AC XY:

42821

AN XY:

74250

show subpopulations

African (AFR)

AF:

0.317

AC:

13133

AN:

41384

American (AMR)

AF:

0.687

AC:

10491

AN:

15270

Ashkenazi Jewish (ASJ)

AF:

0.695

AC:

2410

AN:

3470

East Asian (EAS)

AF:

0.692

AC:

3578

AN:

5170

South Asian (SAS)

AF:

0.648

AC:

3121

AN:

4816

European-Finnish (FIN)

AF:

0.672

AC:

7094

AN:

10552

Middle Eastern (MID)

AF:

0.667

AC:

196

AN:

294

European-Non Finnish (NFE)

AF:

0.664

AC:

45169

AN:

67980

Other (OTH)

AF:

0.607

AC:

1278

AN:

2104

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

1695

3390

5085

6780

8475

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

728

1456

2184

2912

3640

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.637

Hom.:

138372

Bravo

AF:

0.564

Asia WGS

AF:

0.666

AC:

2317

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.89

CADD

Benign

(source)

DANN

Benign

0.66

PhyloP100

1.0

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over