rs3800917

Variant names:

• chr7-2128304-G-A
• rs3800917
• NM_001013836.2:c.1073+20848C>T

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+20848C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.29 in 152,082 control chromosomes in the GnomAD database, including 7,845 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 0.29 (7845 hom., cov: 32)
• Consequence: MAD1L1 NM_001013836.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.620
• Publications: 13 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=-0.9).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.445 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MAD1L1	NM_001013836.2	MANE Select	c.1073+20848C>T		intron	N/A	NP_001013858.1	Q9Y6D9-1
	MAD1L1	NM_001013837.2		c.1073+20848C>T		intron	N/A	NP_001013859.1	Q9Y6D9-1
	MAD1L1	NM_001304523.2		c.1073+20848C>T		intron	N/A	NP_001291452.1	Q9Y6D9-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MAD1L1	ENST00000265854.12	TSL:1 MANE Select	c.1073+20848C>T		intron	N/A	ENSP00000265854.7	Q9Y6D9-1
	MAD1L1	ENST00000406869.5	TSL:1	c.1073+20848C>T		intron	N/A	ENSP00000385334.1	Q9Y6D9-1
	ENSG00000286192	ENST00000651235.1		n.*3833+20792C>T		intron	N/A	ENSP00000498895.1	A0A3B3ITW8

Frequencies

GnomAD3 genomes AF: 0.290 AC: 44078 AN: 151964 Hom.: 7845 Cov.: 32

Gnomad AFR AF: 0.0757

Gnomad AMI AF: 0.197

Gnomad AMR AF: 0.402

Gnomad ASJ AF: 0.302

Gnomad EAS AF: 0.460

Gnomad SAS AF: 0.350

Gnomad FIN AF: 0.315

Gnomad MID AF: 0.222

Gnomad NFE AF: 0.374

Gnomad OTH AF: 0.329

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

GnomAD4 genome AF: 0.290 AC: 44074 AN: 152082 Hom.: 7845 Cov.: 32 AF XY: 0.292 AC XY: 21726 AN XY: 74350

African (AFR) AF: 0.0754 AC: 3133 AN: 41528

American (AMR) AF: 0.403 AC: 6155 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.302 AC: 1050 AN: 3472

East Asian (EAS) AF: 0.461 AC: 2374 AN: 5154

South Asian (SAS) AF: 0.350 AC: 1684 AN: 4818

European-Finnish (FIN) AF: 0.315 AC: 3329 AN: 10574

Middle Eastern (MID) AF: 0.211 AC: 62 AN: 294

European-Non Finnish (NFE) AF: 0.374 AC: 25418 AN: 67940

Other (OTH) AF: 0.328 AC: 690 AN: 2106

Alfa AF: 0.342 Hom.: 3149

Bravo AF: 0.289

Asia WGS AF: 0.389 AC: 1350 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.79
DANN	Benign	0.66
PhyloP100		-0.62
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: rs3800917; hg19: chr7-2167939;