7-1827280-T-C

Variant names:

• chr7-1827280-T-C
• rs13225346
• NM_001013836.2:c.1999-11052A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001013836.2(MAD1L1):​c.1999-11052A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.43 in 151,960 control chromosomes in the GnomAD database, including 14,152 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 0.43 (14152 hom., cov: 35)
• Consequence: MAD1L1 NM_001013836.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.35
• Publications: 9 publications found

Genes affected

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)

ENSG00000286192 (HGNC:):

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.45 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001013836.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MAD1L1	NM_001013836.2	MANE Select	c.1999-11052A>G		intron	N/A	NP_001013858.1
	MAD1L1	NM_001013837.2		c.1999-11052A>G		intron	N/A	NP_001013859.1
	MAD1L1	NM_001304523.2		c.1999-11052A>G		intron	N/A	NP_001291452.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MAD1L1	ENST00000265854.12	TSL:1 MANE Select	c.1999-11052A>G		intron	N/A	ENSP00000265854.7
	MAD1L1	ENST00000406869.5	TSL:1	c.1999-11052A>G		intron	N/A	ENSP00000385334.1
	ENSG00000286192	ENST00000651235.1		n.*4759-11052A>G		intron	N/A	ENSP00000498895.1

Frequencies

GnomAD3 genomes AF: 0.430 AC: 65325 AN: 151840 Hom.: 14131 Cov.: 35

Gnomad AFR AF: 0.420

Gnomad AMI AF: 0.407

Gnomad AMR AF: 0.384

Gnomad ASJ AF: 0.431

Gnomad EAS AF: 0.444

Gnomad SAS AF: 0.295

Gnomad FIN AF: 0.444

Gnomad MID AF: 0.429

Gnomad NFE AF: 0.454

Gnomad OTH AF: 0.412

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

GnomAD4 genome AF: 0.430 AC: 65390 AN: 151960 Hom.: 14152 Cov.: 35 AF XY: 0.427 AC XY: 31712 AN XY: 74270

African (AFR) AF: 0.420 AC: 17398 AN: 41466

American (AMR) AF: 0.384 AC: 5873 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.431 AC: 1495 AN: 3466

East Asian (EAS) AF: 0.443 AC: 2288 AN: 5160

South Asian (SAS) AF: 0.295 AC: 1422 AN: 4818

European-Finnish (FIN) AF: 0.444 AC: 4687 AN: 10546

Middle Eastern (MID) AF: 0.448 AC: 129 AN: 288

European-Non Finnish (NFE) AF: 0.454 AC: 30848 AN: 67904

Other (OTH) AF: 0.416 AC: 880 AN: 2114

Alfa AF: 0.430 Hom.: 19258

Bravo AF: 0.427

Asia WGS AF: 0.400 AC: 1390 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	1.4
DANN	Benign	0.56
PhyloP100		-1.3
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs13225346; hg19: chr7-1866916; COSMIC: COSV56229303;