rs13244625

Variant names:

• chr7-2167055-A-G
• rs13244625
• NM_001013836.2:c.987-17817T>C

Variant summary

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

The NM_001013836.2(MAD1L1):​c.987-17817T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.146 in 152,240 control chromosomes in the GnomAD database, including 1,840 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 0.15 (1840 hom., cov: 32)
• Consequence: MAD1L1 NM_001013836.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.300
• Publications: 2 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=-0.98).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.201 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MAD1L1	NM_001013836.2	c.987-17817T>C		intron_variant	Intron 10 of 18	ENST00000265854.12	NP_001013858.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MAD1L1	ENST00000265854.12	c.987-17817T>C		intron_variant	Intron 10 of 18	1	NM_001013836.2	ENSP00000265854.7
ENSG00000286192	ENST00000651235.1	n.*3691-17817T>C		intron_variant	Intron 15 of 23			ENSP00000498895.1

Frequencies

GnomAD3 genomes AF: 0.146 AC: 22217 AN: 152122 Hom.: 1838 Cov.: 32

Gnomad AFR AF: 0.0759

Gnomad AMI AF: 0.202

Gnomad AMR AF: 0.180

Gnomad ASJ AF: 0.277

Gnomad EAS AF: 0.0533

Gnomad SAS AF: 0.210

Gnomad FIN AF: 0.129

Gnomad MID AF: 0.266

Gnomad NFE AF: 0.178

Gnomad OTH AF: 0.167

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

GnomAD4 genome AF: 0.146 AC: 22231 AN: 152240 Hom.: 1840 Cov.: 32 AF XY: 0.143 AC XY: 10670 AN XY: 74442

African (AFR) AF: 0.0758 AC: 3151 AN: 41552

American (AMR) AF: 0.180 AC: 2749 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.277 AC: 960 AN: 3470

East Asian (EAS) AF: 0.0528 AC: 274 AN: 5186

South Asian (SAS) AF: 0.211 AC: 1020 AN: 4824

European-Finnish (FIN) AF: 0.129 AC: 1370 AN: 10618

Middle Eastern (MID) AF: 0.269 AC: 79 AN: 294

European-Non Finnish (NFE) AF: 0.178 AC: 12095 AN: 67988

Other (OTH) AF: 0.165 AC: 350 AN: 2116

Alfa AF: 0.154 Hom.: 319

Bravo AF: 0.149

Asia WGS AF: 0.129 AC: 447 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	3.7
DANN	Benign	0.44
PhyloP100		0.30
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: rs13244625; hg19: chr7-2206690; COSMIC: COSV56233784;