NM_001013836.2:c.1073+4727A>G

Variant names:

• chr7-2144425-T-C
• rs4721441
• NM_001013836.2:c.1073+4727A>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.1073+4727A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.336 in 152,010 control chromosomes in the GnomAD database, including 8,930 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 0.34 (8930 hom., cov: 32)
• Consequence: MAD1L1 NM_001013836.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.33
• Publications: 7 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=-0.99).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.504 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MAD1L1	NM_001013836.2	c.1073+4727A>G		intron_variant	Intron 11 of 18	ENST00000265854.12	NP_001013858.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MAD1L1	ENST00000265854.12	c.1073+4727A>G		intron_variant	Intron 11 of 18	1	NM_001013836.2	ENSP00000265854.7
ENSG00000286192	ENST00000651235.1	n.*3833+4671A>G		intron_variant	Intron 16 of 23			ENSP00000498895.1

Frequencies

GnomAD3 genomes AF: 0.336 AC: 51048 AN: 151892 Hom.: 8920 Cov.: 32

Gnomad AFR AF: 0.258

Gnomad AMI AF: 0.190

Gnomad AMR AF: 0.415

Gnomad ASJ AF: 0.277

Gnomad EAS AF: 0.520

Gnomad SAS AF: 0.344

Gnomad FIN AF: 0.312

Gnomad MID AF: 0.229

Gnomad NFE AF: 0.360

Gnomad OTH AF: 0.357

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

GnomAD4 genome AF: 0.336 AC: 51091 AN: 152010 Hom.: 8930 Cov.: 32 AF XY: 0.337 AC XY: 25081 AN XY: 74318

African (AFR) AF: 0.258 AC: 10718 AN: 41464

American (AMR) AF: 0.416 AC: 6354 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.277 AC: 962 AN: 3468

East Asian (EAS) AF: 0.521 AC: 2680 AN: 5146

South Asian (SAS) AF: 0.343 AC: 1655 AN: 4820

European-Finnish (FIN) AF: 0.312 AC: 3294 AN: 10562

Middle Eastern (MID) AF: 0.216 AC: 63 AN: 292

European-Non Finnish (NFE) AF: 0.360 AC: 24441 AN: 67948

Other (OTH) AF: 0.356 AC: 752 AN: 2114

Alfa AF: 0.357 Hom.: 3034

Bravo AF: 0.343

Asia WGS AF: 0.415 AC: 1442 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
CADD	Benign	1.1
DANN	Benign	0.33
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: rs4721441; hg19: chr7-2184060;