Genetic Variant ENSG00000286192:n.*2121-331T>C (chr7-2233301-A-G) – ACMG Classification: Benign (-12 pts)

Variant summary

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

The ENST00000651235.1(ENSG00000286192):n.*2121-331T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.347 in 152,226 control chromosomes in the GnomAD database, including 9,399 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 0.35 ( 9393 hom., cov: 33)

Exomes 𝑓: 0.43 ( 6 hom. )

Consequence

ENSG00000286192
ENST00000651235.1 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.215

Publications

21 publications found

Variant links:

Genes affected

ENSG00000286192 (HGNC:):

ENSG00000286192 links:

MAD1L1 (HGNC:6762): (mitotic arrest deficient 1 like 1) MAD1L1 is a component of the mitotic spindle-assembly checkpoint that prevents the onset of anaphase until all chromosome are properly aligned at the metaphase plate. MAD1L1 functions as a homodimer and interacts with MAD2L1. MAD1L1 may play a role in cell cycle control and tumor suppression. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jan 2015]

MAD1L1 Gene-Disease associations (from GenCC):

mosaic variegated aneuploidy syndrome 7 with inflammation and tumor predisposition
Inheritance: AR Classification: LIMITED Submitted by: Ambry Genetics
familial prostate carcinoma
Inheritance: Unknown Classification: LIMITED Submitted by: Labcorp Genetics (formerly Invitae)

MAD1L1 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=-0.8).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.497 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	Protein	UniProt
ENSG00000286192	ENST00000651235.1 link	n.*2121-331T>C	intron_variant	Intron 4 of 23		ENSP00000498895.1	A0A3B3ITW8
ENSG00000294599	ENST00000724666.1 link	n.440+772A>G	intron_variant	Intron 1 of 1
ENSG00000294599	ENST00000724667.1 link	n.80-254A>G	intron_variant	Intron 1 of 1
MAD1L1	ENST00000406869.5 link	c.-616T>C	upstream_gene_variant		1	ENSP00000385334.1	Q9Y6D9-1

Frequencies

GnomAD3 genomes

AF:

0.347

AC:

52719

AN:

152048

Hom.:

9388

Cov.:

show subpopulations

Gnomad AFR

AF:

0.328

Gnomad AMI

AF:

0.221

Gnomad AMR

AF:

0.385

Gnomad ASJ

AF:

0.262

Gnomad EAS

AF:

0.512

Gnomad SAS

AF:

0.331

Gnomad FIN

AF:

0.276

Gnomad MID

AF:

0.199

Gnomad NFE

AF:

0.355

Gnomad OTH

AF:

0.357

GnomAD4 exome

AF:

0.433

AC:

AN:

Hom.:

AF XY:

0.413

AC XY:

AN XY:

show subpopulations

African (AFR)

AC:

AN:

American (AMR)

AC:

AN:

Ashkenazi Jewish (ASJ)

AC:

AN:

East Asian (EAS)

AC:

AN:

South Asian (SAS)

AF:

0.750

AC:

AN:

European-Finnish (FIN)

AF:

0.500

AC:

AN:

Middle Eastern (MID)

AC:

AN:

European-Non Finnish (NFE)

AF:

0.421

AC:

AN:

Other (OTH)

AF:

0.300

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.532

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Hom

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.347

AC:

52739

AN:

152166

Hom.:

9393

Cov.:

AF XY:

0.346

AC XY:

25726

AN XY:

74382

show subpopulations

African (AFR)

AF:

0.328

AC:

13615

AN:

41516

American (AMR)

AF:

0.385

AC:

5889

AN:

15302

Ashkenazi Jewish (ASJ)

AF:

0.262

AC:

907

AN:

3466

East Asian (EAS)

AF:

0.513

AC:

2644

AN:

5156

South Asian (SAS)

AF:

0.331

AC:

1597

AN:

4828

European-Finnish (FIN)

AF:

0.276

AC:

2925

AN:

10584

Middle Eastern (MID)

AF:

0.194

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.355

AC:

24154

AN:

67996

Other (OTH)

AF:

0.355

AC:

749

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

1781

3562

5344

7125

8906

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

532

1064

1596

2128

2660

<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:

0.354

Hom.:

13822

Bravo

AF:

0.358

Asia WGS

AF:

0.439

AC:

1525

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.80

CADD

Benign

(source)

DANN

Benign

0.69

PhyloP100

0.21

PromoterAI

-0.012

Neutral

(source)

Mutation Taster

=100/0

polymorphism

(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

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over