rs7804190

Variant names:

• chr7-1954264-A-C
• rs7804190
• NM_001013836.2:c.1596+3365T>G

Your query was ambiguous. Multiple possible variants found:

• chr7-1954264-A-C
• chr7-1954264-A-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.1596+3365T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.614 in 152,084 control chromosomes in the GnomAD database, including 28,800 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 0.61 (28800 hom., cov: 32)
• Consequence: MAD1L1 NM_001013836.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.777
• Publications: 11 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 (SAS) allele frequency at 95% confidence interval = 0.682 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MAD1L1	NM_001013836.2	MANE Select	c.1596+3365T>G		intron	N/A	NP_001013858.1	Q9Y6D9-1
	MAD1L1	NM_001013837.2		c.1596+3365T>G		intron	N/A	NP_001013859.1	Q9Y6D9-1
	MAD1L1	NM_001304523.2		c.1596+3365T>G		intron	N/A	NP_001291452.1	Q9Y6D9-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MAD1L1	ENST00000265854.12	TSL:1 MANE Select	c.1596+3365T>G		intron	N/A	ENSP00000265854.7	Q9Y6D9-1
	MAD1L1	ENST00000406869.5	TSL:1	c.1596+3365T>G		intron	N/A	ENSP00000385334.1	Q9Y6D9-1
	ENSG00000286192	ENST00000651235.1		n.*4356+3365T>G		intron	N/A	ENSP00000498895.1	A0A3B3ITW8

Frequencies

GnomAD3 genomes AF: 0.614 AC: 93262 AN: 151966 Hom.: 28794 Cov.: 32

Gnomad AFR AF: 0.564

Gnomad AMI AF: 0.421

Gnomad AMR AF: 0.627

Gnomad ASJ AF: 0.653

Gnomad EAS AF: 0.585

Gnomad SAS AF: 0.701

Gnomad FIN AF: 0.632

Gnomad MID AF: 0.592

Gnomad NFE AF: 0.634

Gnomad OTH AF: 0.641

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

GnomAD4 genome AF: 0.614 AC: 93310 AN: 152084 Hom.: 28800 Cov.: 32 AF XY: 0.616 AC XY: 45774 AN XY: 74334

African (AFR) AF: 0.564 AC: 23387 AN: 41502

American (AMR) AF: 0.627 AC: 9590 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.653 AC: 2266 AN: 3472

East Asian (EAS) AF: 0.586 AC: 3018 AN: 5148

South Asian (SAS) AF: 0.701 AC: 3381 AN: 4820

European-Finnish (FIN) AF: 0.632 AC: 6692 AN: 10584

Middle Eastern (MID) AF: 0.578 AC: 170 AN: 294

European-Non Finnish (NFE) AF: 0.634 AC: 43081 AN: 67952

Other (OTH) AF: 0.636 AC: 1341 AN: 2108

Alfa AF: 0.625 Hom.: 96792

Bravo AF: 0.608

Asia WGS AF: 0.639 AC: 2223 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.48
DANN	Benign	0.45
PhyloP100		-0.78
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: rs7804190; hg19: chr7-1993899;