chr7-1964786-C-T

Variant names:

• chr7-1964786-C-T
• rs12666575
• NM_001013836.2:c.1506-7067G>A

Variant summary

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

The NM_001013836.2(MAD1L1):​c.1506-7067G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.293 in 152,152 control chromosomes in the GnomAD database, including 7,835 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 (7835 hom., cov: 33)
• Consequence: MAD1L1 NM_001013836.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.182
• Publications: 43 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=-0.92).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.455 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MAD1L1	NM_001013836.2	c.1506-7067G>A		intron_variant	Intron 15 of 18	ENST00000265854.12	NP_001013858.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MAD1L1	ENST00000265854.12	c.1506-7067G>A		intron_variant	Intron 15 of 18	1	NM_001013836.2	ENSP00000265854.7
ENSG00000286192	ENST00000651235.1	n.*4266-7067G>A		intron_variant	Intron 20 of 23			ENSP00000498895.1

Frequencies

GnomAD3 genomes AF: 0.293 AC: 44564 AN: 152034 Hom.: 7832 Cov.: 33

Gnomad AFR AF: 0.0902

Gnomad AMI AF: 0.211

Gnomad AMR AF: 0.404

Gnomad ASJ AF: 0.346

Gnomad EAS AF: 0.470

Gnomad SAS AF: 0.319

Gnomad FIN AF: 0.318

Gnomad MID AF: 0.250

Gnomad NFE AF: 0.370

Gnomad OTH AF: 0.331

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

GnomAD4 genome AF: 0.293 AC: 44559 AN: 152152 Hom.: 7835 Cov.: 33 AF XY: 0.295 AC XY: 21939 AN XY: 74368

African (AFR) AF: 0.0900 AC: 3736 AN: 41534

American (AMR) AF: 0.405 AC: 6186 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.346 AC: 1202 AN: 3472

East Asian (EAS) AF: 0.471 AC: 2437 AN: 5174

South Asian (SAS) AF: 0.318 AC: 1534 AN: 4824

European-Finnish (FIN) AF: 0.318 AC: 3352 AN: 10556

Middle Eastern (MID) AF: 0.235 AC: 69 AN: 294

European-Non Finnish (NFE) AF: 0.370 AC: 25157 AN: 67984

Other (OTH) AF: 0.329 AC: 694 AN: 2112

Alfa AF: 0.350 Hom.: 42409

Bravo AF: 0.293

Asia WGS AF: 0.368 AC: 1277 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	6.3
DANN	Benign	0.53
PhyloP100		0.18
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: rs12666575; hg19: chr7-2004421;