7-2110332-A-G

Variant names:

• chr7-2110332-A-G
• rs10224497
• NM_001013836.2:c.1073+38820T>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+38820T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.411 in 152,116 control chromosomes in the GnomAD database, including 13,387 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 0.41 (13387 hom., cov: 33)
• Consequence: MAD1L1 NM_001013836.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.486
• Publications: 21 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=-0.82).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.588 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.1073+38820T>C		intron	N/A	NP_001013858.1
	MAD1L1	NM_001013837.2		c.1073+38820T>C		intron	N/A	NP_001013859.1
	MAD1L1	NM_001304523.2		c.1073+38820T>C		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.1073+38820T>C		intron	N/A	ENSP00000265854.7
	MAD1L1	ENST00000406869.5	TSL:1	c.1073+38820T>C		intron	N/A	ENSP00000385334.1
	ENSG00000286192	ENST00000651235.1		n.*3833+38764T>C		intron	N/A	ENSP00000498895.1

Frequencies

GnomAD3 genomes AF: 0.411 AC: 62534 AN: 151998 Hom.: 13383 Cov.: 33

Gnomad AFR AF: 0.319

Gnomad AMI AF: 0.329

Gnomad AMR AF: 0.509

Gnomad ASJ AF: 0.366

Gnomad EAS AF: 0.605

Gnomad SAS AF: 0.461

Gnomad FIN AF: 0.404

Gnomad MID AF: 0.288

Gnomad NFE AF: 0.432

Gnomad OTH AF: 0.421

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

GnomAD4 genome AF: 0.411 AC: 62562 AN: 152116 Hom.: 13387 Cov.: 33 AF XY: 0.414 AC XY: 30798 AN XY: 74376

African (AFR) AF: 0.319 AC: 13229 AN: 41452

American (AMR) AF: 0.509 AC: 7784 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.366 AC: 1268 AN: 3466

East Asian (EAS) AF: 0.605 AC: 3135 AN: 5180

South Asian (SAS) AF: 0.460 AC: 2215 AN: 4820

European-Finnish (FIN) AF: 0.404 AC: 4277 AN: 10592

Middle Eastern (MID) AF: 0.279 AC: 82 AN: 294

European-Non Finnish (NFE) AF: 0.432 AC: 29388 AN: 67992

Other (OTH) AF: 0.419 AC: 884 AN: 2112

Alfa AF: 0.421 Hom.: 15055

Bravo AF: 0.417

Asia WGS AF: 0.511 AC: 1777 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	0.049
DANN	Benign	0.45
PhyloP100		-0.49
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: rs10224497; hg19: chr7-2149967; COSMIC: COSV56230161; COSMIC: COSV56230161;