rs3778994

Variant names:

• chr7-2136220-C-A
• rs3778994
• NM_001013836.2:c.1073+12932G>T

Your query was ambiguous. Multiple possible variants found:

• chr7-2136220-C-A
• chr7-2136220-C-G
• chr7-2136220-C-T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000265854.12(MAD1L1):​c.1073+12932G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.351 in 152,134 control chromosomes in the GnomAD database, including 9,973 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 0.35 (9973 hom., cov: 33)
• Consequence: MAD1L1 ENST00000265854.12 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.670
• Publications: 16 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 (EAS) allele frequency at 95% confidence interval = 0.496 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000265854.12. 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.1073+12932G>T		intron	N/A	NP_001013858.1
	MAD1L1	NM_001013837.2		c.1073+12932G>T		intron	N/A	NP_001013859.1
	MAD1L1	NM_001304523.2		c.1073+12932G>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.1073+12932G>T		intron	N/A	ENSP00000265854.7
	MAD1L1	ENST00000406869.5	TSL:1	c.1073+12932G>T		intron	N/A	ENSP00000385334.1
	ENSG00000286192	ENST00000651235.1		n.*3833+12876G>T		intron	N/A	ENSP00000498895.1

Frequencies

GnomAD3 genomes AF: 0.351 AC: 53411 AN: 152018 Hom.: 9967 Cov.: 33

Gnomad AFR AF: 0.231

Gnomad AMI AF: 0.317

Gnomad AMR AF: 0.452

Gnomad ASJ AF: 0.300

Gnomad EAS AF: 0.512

Gnomad SAS AF: 0.412

Gnomad FIN AF: 0.332

Gnomad MID AF: 0.282

Gnomad NFE AF: 0.391

Gnomad OTH AF: 0.375

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

GnomAD4 genome AF: 0.351 AC: 53439 AN: 152134 Hom.: 9973 Cov.: 33 AF XY: 0.354 AC XY: 26331 AN XY: 74372

African (AFR) AF: 0.231 AC: 9585 AN: 41512

American (AMR) AF: 0.452 AC: 6908 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.300 AC: 1040 AN: 3470

East Asian (EAS) AF: 0.512 AC: 2651 AN: 5176

South Asian (SAS) AF: 0.411 AC: 1979 AN: 4820

European-Finnish (FIN) AF: 0.332 AC: 3510 AN: 10564

Middle Eastern (MID) AF: 0.264 AC: 77 AN: 292

European-Non Finnish (NFE) AF: 0.391 AC: 26613 AN: 68000

Other (OTH) AF: 0.373 AC: 787 AN: 2112

Alfa AF: 0.382 Hom.: 20430

Bravo AF: 0.358

Asia WGS AF: 0.430 AC: 1493 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	0.29
DANN	Benign	0.54
PhyloP100		-0.67
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: rs3778994; hg19: chr7-2175855;