rs4332037

Variant names:

• chr7-1911173-C-T
• rs4332037
• NM_001013836.2:c.1808-12783G>A

Variant summary

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

The NM_001013836.2(MAD1L1):​c.1808-12783G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.187 in 152,102 control chromosomes in the GnomAD database, including 2,783 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 0.19 (2783 hom., cov: 32)
• Consequence: MAD1L1 NM_001013836.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.60
• Publications: 30 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 (SAS) allele frequency at 95% confidence interval = 0.266 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MAD1L1	NM_001013836.2	c.1808-12783G>A		intron_variant	Intron 17 of 18	ENST00000265854.12	NP_001013858.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MAD1L1	ENST00000265854.12	c.1808-12783G>A		intron_variant	Intron 17 of 18	1	NM_001013836.2	ENSP00000265854.7
ENSG00000286192	ENST00000651235.1	n.*4568-12783G>A		intron_variant	Intron 22 of 23			ENSP00000498895.1

Frequencies

GnomAD3 genomes AF: 0.187 AC: 28403 AN: 151984 Hom.: 2778 Cov.: 32

Gnomad AFR AF: 0.161

Gnomad AMI AF: 0.159

Gnomad AMR AF: 0.161

Gnomad ASJ AF: 0.209

Gnomad EAS AF: 0.112

Gnomad SAS AF: 0.276

Gnomad FIN AF: 0.267

Gnomad MID AF: 0.241

Gnomad NFE AF: 0.194

Gnomad OTH AF: 0.193

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

GnomAD4 genome AF: 0.187 AC: 28423 AN: 152102 Hom.: 2783 Cov.: 32 AF XY: 0.191 AC XY: 14177 AN XY: 74342

African (AFR) AF: 0.161 AC: 6692 AN: 41486

American (AMR) AF: 0.161 AC: 2461 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.209 AC: 725 AN: 3470

East Asian (EAS) AF: 0.112 AC: 576 AN: 5162

South Asian (SAS) AF: 0.278 AC: 1339 AN: 4812

European-Finnish (FIN) AF: 0.267 AC: 2830 AN: 10582

Middle Eastern (MID) AF: 0.235 AC: 69 AN: 294

European-Non Finnish (NFE) AF: 0.194 AC: 13185 AN: 67988

Other (OTH) AF: 0.190 AC: 401 AN: 2110

Alfa AF: 0.191 Hom.: 8551

Bravo AF: 0.172

Asia WGS AF: 0.184 AC: 640 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	2.5
DANN	Benign	0.46
PhyloP100		-1.6
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: rs4332037; hg19: chr7-1950809;