chr7-2001797-A-G

Variant names:

• chr7-2001797-A-G
• rs1107592
• NM_001013836.2:c.1416+268T>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.1416+268T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.374 in 152,118 control chromosomes in the GnomAD database, including 11,009 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 0.37 (11009 hom., cov: 34)
• Consequence: MAD1L1 NM_001013836.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.681
• Publications: 33 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=-1.01).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.548 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MAD1L1	NM_001013836.2	c.1416+268T>C		intron_variant	Intron 14 of 18	ENST00000265854.12	NP_001013858.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MAD1L1	ENST00000265854.12	c.1416+268T>C		intron_variant	Intron 14 of 18	1	NM_001013836.2	ENSP00000265854.7
ENSG00000286192	ENST00000651235.1	n.*4176+268T>C		intron_variant	Intron 19 of 23			ENSP00000498895.1

Frequencies

GnomAD3 genomes AF: 0.374 AC: 56852 AN: 152000 Hom.: 11000 Cov.: 34

Gnomad AFR AF: 0.306

Gnomad AMI AF: 0.204

Gnomad AMR AF: 0.465

Gnomad ASJ AF: 0.391

Gnomad EAS AF: 0.564

Gnomad SAS AF: 0.343

Gnomad FIN AF: 0.335

Gnomad MID AF: 0.253

Gnomad NFE AF: 0.390

Gnomad OTH AF: 0.394

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

GnomAD4 genome AF: 0.374 AC: 56894 AN: 152118 Hom.: 11009 Cov.: 34 AF XY: 0.374 AC XY: 27786 AN XY: 74366

African (AFR) AF: 0.306 AC: 12714 AN: 41500

American (AMR) AF: 0.465 AC: 7108 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.391 AC: 1357 AN: 3470

East Asian (EAS) AF: 0.565 AC: 2912 AN: 5156

South Asian (SAS) AF: 0.343 AC: 1657 AN: 4828

European-Finnish (FIN) AF: 0.335 AC: 3549 AN: 10590

Middle Eastern (MID) AF: 0.238 AC: 70 AN: 294

European-Non Finnish (NFE) AF: 0.390 AC: 26515 AN: 67964

Other (OTH) AF: 0.391 AC: 826 AN: 2110

Alfa AF: 0.386 Hom.: 18766

Bravo AF: 0.382

Asia WGS AF: 0.443 AC: 1541 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	0.83
DANN	Benign	0.18
PhyloP100		-0.68
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs1107592; hg19: chr7-2041432;