7-2118755-A-G

Variant names:

• chr7-2118755-A-G
• rs10239050
• NM_001013836.2:c.1073+30397T>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.1073+30397T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.354 in 152,006 control chromosomes in the GnomAD database, including 10,347 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 (10347 hom., cov: 32)
• Consequence: MAD1L1 NM_001013836.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.280
• Publications: 10 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=-1.0).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.587 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MAD1L1	NM_001013836.2	c.1073+30397T>C		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+30397T>C		intron_variant	Intron 11 of 18	1	NM_001013836.2	ENSP00000265854.7
ENSG00000286192	ENST00000651235.1	n.*3833+30341T>C		intron_variant	Intron 16 of 23			ENSP00000498895.1

Frequencies

GnomAD3 genomes AF: 0.354 AC: 53793 AN: 151888 Hom.: 10350 Cov.: 32

Gnomad AFR AF: 0.214

Gnomad AMI AF: 0.201

Gnomad AMR AF: 0.456

Gnomad ASJ AF: 0.341

Gnomad EAS AF: 0.605

Gnomad SAS AF: 0.372

Gnomad FIN AF: 0.381

Gnomad MID AF: 0.231

Gnomad NFE AF: 0.395

Gnomad OTH AF: 0.381

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

GnomAD4 genome AF: 0.354 AC: 53806 AN: 152006 Hom.: 10347 Cov.: 32 AF XY: 0.357 AC XY: 26519 AN XY: 74272

African (AFR) AF: 0.214 AC: 8889 AN: 41498

American (AMR) AF: 0.456 AC: 6974 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.341 AC: 1183 AN: 3468

East Asian (EAS) AF: 0.605 AC: 3104 AN: 5130

South Asian (SAS) AF: 0.371 AC: 1788 AN: 4816

European-Finnish (FIN) AF: 0.381 AC: 4012 AN: 10544

Middle Eastern (MID) AF: 0.221 AC: 65 AN: 294

European-Non Finnish (NFE) AF: 0.395 AC: 26807 AN: 67940

Other (OTH) AF: 0.379 AC: 801 AN: 2114

Alfa AF: 0.389 Hom.: 10011

Bravo AF: 0.356

Asia WGS AF: 0.466 AC: 1619 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	1.8
DANN	Benign	0.37
PhyloP100		-0.28
RBP_binding_hub_radar		0.67
RBP_regulation_power_radar		1.8
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: rs10239050; hg19: chr7-2158390;