7-1993168-C-T

Variant names:

• chr7-1993168-C-T
• rs11764590
• NM_001013836.2:c.1416+8897G>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.1416+8897G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.169 in 152,256 control chromosomes in the GnomAD database, including 2,710 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 0.17 (2710 hom., cov: 33)
• Consequence: MAD1L1 NM_001013836.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.522
• Publications: 20 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 (SAS) allele frequency at 95% confidence interval = 0.294 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MAD1L1	NM_001013836.2	c.1416+8897G>A		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+8897G>A		intron_variant	Intron 14 of 18	1	NM_001013836.2	ENSP00000265854.7
ENSG00000286192	ENST00000651235.1	n.*4176+8897G>A		intron_variant	Intron 19 of 23			ENSP00000498895.1

Frequencies

GnomAD3 genomes AF: 0.169 AC: 25695 AN: 152138 Hom.: 2708 Cov.: 33

Gnomad AFR AF: 0.0584

Gnomad AMI AF: 0.185

Gnomad AMR AF: 0.161

Gnomad ASJ AF: 0.232

Gnomad EAS AF: 0.102

Gnomad SAS AF: 0.306

Gnomad FIN AF: 0.318

Gnomad MID AF: 0.297

Gnomad NFE AF: 0.206

Gnomad OTH AF: 0.181

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

GnomAD4 genome AF: 0.169 AC: 25685 AN: 152256 Hom.: 2710 Cov.: 33 AF XY: 0.175 AC XY: 13047 AN XY: 74440

African (AFR) AF: 0.0582 AC: 2420 AN: 41554

American (AMR) AF: 0.160 AC: 2454 AN: 15306

Ashkenazi Jewish (ASJ) AF: 0.232 AC: 805 AN: 3468

East Asian (EAS) AF: 0.101 AC: 526 AN: 5188

South Asian (SAS) AF: 0.308 AC: 1484 AN: 4826

European-Finnish (FIN) AF: 0.318 AC: 3368 AN: 10580

Middle Eastern (MID) AF: 0.299 AC: 88 AN: 294

European-Non Finnish (NFE) AF: 0.206 AC: 13995 AN: 68016

Other (OTH) AF: 0.178 AC: 377 AN: 2114

Alfa AF: 0.199 Hom.: 4120

Bravo AF: 0.148

Asia WGS AF: 0.187 AC: 653 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	1.6
DANN	Benign	0.39
PhyloP100		-0.52
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: rs11764590; hg19: chr7-2032803;