rs10278591

Variant names:

• chr7-1881726-C-T
• rs10278591
• NM_001013836.2:c.1998+16474G>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.1998+16474G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.313 in 152,058 control chromosomes in the GnomAD database, including 9,200 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 0.31 (9200 hom., cov: 33)
• Consequence: MAD1L1 NM_001013836.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.34
• Publications: 10 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=-0.98).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.544 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MAD1L1	NM_001013836.2	c.1998+16474G>A		intron_variant	Intron 18 of 18	ENST00000265854.12	NP_001013858.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MAD1L1	ENST00000265854.12	c.1998+16474G>A		intron_variant	Intron 18 of 18	1	NM_001013836.2	ENSP00000265854.7
ENSG00000286192	ENST00000651235.1	n.*4758+16474G>A		intron_variant	Intron 23 of 23			ENSP00000498895.1

Frequencies

GnomAD3 genomes AF: 0.313 AC: 47503 AN: 151940 Hom.: 9189 Cov.: 33

Gnomad AFR AF: 0.550

Gnomad AMI AF: 0.163

Gnomad AMR AF: 0.235

Gnomad ASJ AF: 0.251

Gnomad EAS AF: 0.197

Gnomad SAS AF: 0.365

Gnomad FIN AF: 0.276

Gnomad MID AF: 0.275

Gnomad NFE AF: 0.202

Gnomad OTH AF: 0.302

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

GnomAD4 genome AF: 0.313 AC: 47550 AN: 152058 Hom.: 9200 Cov.: 33 AF XY: 0.315 AC XY: 23453 AN XY: 74352

African (AFR) AF: 0.550 AC: 22781 AN: 41430

American (AMR) AF: 0.235 AC: 3589 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.251 AC: 872 AN: 3468

East Asian (EAS) AF: 0.196 AC: 1015 AN: 5176

South Asian (SAS) AF: 0.367 AC: 1768 AN: 4816

European-Finnish (FIN) AF: 0.276 AC: 2927 AN: 10588

Middle Eastern (MID) AF: 0.269 AC: 79 AN: 294

European-Non Finnish (NFE) AF: 0.202 AC: 13742 AN: 67978

Other (OTH) AF: 0.299 AC: 629 AN: 2106

Alfa AF: 0.243 Hom.: 4125

Bravo AF: 0.315

Asia WGS AF: 0.298 AC: 1037 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	0.70
DANN	Benign	0.43
PhyloP100		-1.3
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: rs10278591; hg19: chr7-1921362;