rs3778991

Variant names:

• chr7-2132820-G-A
• rs3778991
• NM_001013836.2:c.1073+16332C>T

Your query was ambiguous. Multiple possible variants found:

• chr7-2132820-G-A
• chr7-2132820-G-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+16332C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.281 in 152,152 control chromosomes in the GnomAD database, including 7,453 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 0.28 (7453 hom., cov: 33)
• Consequence: MAD1L1 NM_001013836.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.514
• Publications: 15 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=-0.89).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.49 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+16332C>T		intron	N/A	NP_001013858.1
	MAD1L1	NM_001013837.2		c.1073+16332C>T		intron	N/A	NP_001013859.1
	MAD1L1	NM_001304523.2		c.1073+16332C>T		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+16332C>T		intron	N/A	ENSP00000265854.7
	MAD1L1	ENST00000406869.5	TSL:1	c.1073+16332C>T		intron	N/A	ENSP00000385334.1
	ENSG00000286192	ENST00000651235.1		n.*3833+16276C>T		intron	N/A	ENSP00000498895.1

Frequencies

GnomAD3 genomes AF: 0.281 AC: 42763 AN: 152034 Hom.: 7453 Cov.: 33

Gnomad AFR AF: 0.0724

Gnomad AMI AF: 0.189

Gnomad AMR AF: 0.393

Gnomad ASJ AF: 0.276

Gnomad EAS AF: 0.506

Gnomad SAS AF: 0.341

Gnomad FIN AF: 0.312

Gnomad MID AF: 0.213

Gnomad NFE AF: 0.358

Gnomad OTH AF: 0.319

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

GnomAD4 genome AF: 0.281 AC: 42759 AN: 152152 Hom.: 7453 Cov.: 33 AF XY: 0.285 AC XY: 21188 AN XY: 74382

African (AFR) AF: 0.0721 AC: 2996 AN: 41540

American (AMR) AF: 0.393 AC: 6013 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.276 AC: 956 AN: 3468

East Asian (EAS) AF: 0.506 AC: 2608 AN: 5156

South Asian (SAS) AF: 0.341 AC: 1643 AN: 4824

European-Finnish (FIN) AF: 0.312 AC: 3303 AN: 10582

Middle Eastern (MID) AF: 0.202 AC: 59 AN: 292

European-Non Finnish (NFE) AF: 0.358 AC: 24339 AN: 67984

Other (OTH) AF: 0.318 AC: 670 AN: 2108

Alfa AF: 0.333 Hom.: 25540

Bravo AF: 0.280

Asia WGS AF: 0.398 AC: 1384 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	7.2
DANN	Benign	0.82
PhyloP100		0.51
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: rs3778991; hg19: chr7-2172455;