7-1897625-G-A

Variant names:

• chr7-1897625-G-A
• rs10267593
• NM_001013836.2:c.1998+575C>T

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+575C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.252 in 152,214 control chromosomes in the GnomAD database, including 5,500 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 0.25 (5500 hom., cov: 34)
• Consequence: MAD1L1 NM_001013836.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.378
• 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=-0.89).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.382 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.1998+575C>T		intron	N/A	NP_001013858.1
	MAD1L1	NM_001013837.2		c.1998+575C>T		intron	N/A	NP_001013859.1
	MAD1L1	NM_001304523.2		c.1998+575C>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.1998+575C>T		intron	N/A	ENSP00000265854.7
	MAD1L1	ENST00000406869.5	TSL:1	c.1998+575C>T		intron	N/A	ENSP00000385334.1
	ENSG00000286192	ENST00000651235.1		n.*4758+575C>T		intron	N/A	ENSP00000498895.1

Frequencies

GnomAD3 genomes AF: 0.252 AC: 38280 AN: 152096 Hom.: 5499 Cov.: 34

Gnomad AFR AF: 0.387

Gnomad AMI AF: 0.159

Gnomad AMR AF: 0.188

Gnomad ASJ AF: 0.216

Gnomad EAS AF: 0.112

Gnomad SAS AF: 0.321

Gnomad FIN AF: 0.266

Gnomad MID AF: 0.269

Gnomad NFE AF: 0.190

Gnomad OTH AF: 0.249

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

GnomAD4 genome AF: 0.252 AC: 38305 AN: 152214 Hom.: 5500 Cov.: 34 AF XY: 0.255 AC XY: 18946 AN XY: 74408

African (AFR) AF: 0.387 AC: 16080 AN: 41532

American (AMR) AF: 0.188 AC: 2878 AN: 15302

Ashkenazi Jewish (ASJ) AF: 0.216 AC: 749 AN: 3468

East Asian (EAS) AF: 0.112 AC: 580 AN: 5180

South Asian (SAS) AF: 0.323 AC: 1558 AN: 4820

European-Finnish (FIN) AF: 0.266 AC: 2819 AN: 10590

Middle Eastern (MID) AF: 0.262 AC: 77 AN: 294

European-Non Finnish (NFE) AF: 0.190 AC: 12899 AN: 68000

Other (OTH) AF: 0.246 AC: 520 AN: 2116

Alfa AF: 0.215 Hom.: 1977

Bravo AF: 0.248

Asia WGS AF: 0.223 AC: 776 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	0.62
DANN	Benign	0.82
PhyloP100		-0.38
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: rs10267593; hg19: chr7-1937261;