7-1929317-T-C

Variant names:

• chr7-1929317-T-C
• rs12699477
• NM_001013836.2:c.1807+7370A>G

Variant summary

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

The NM_001013836.2(MAD1L1):​c.1807+7370A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.291 in 152,142 control chromosomes in the GnomAD database, including 7,714 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 0.29 (7714 hom., cov: 33)
• Consequence: MAD1L1 NM_001013836.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.211
• Publications: 35 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=-0.82).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.453 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MAD1L1	NM_001013836.2	c.1807+7370A>G		intron_variant	Intron 17 of 18	ENST00000265854.12	NP_001013858.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MAD1L1	ENST00000265854.12	c.1807+7370A>G		intron_variant	Intron 17 of 18	1	NM_001013836.2	ENSP00000265854.7
ENSG00000286192	ENST00000651235.1	n.*4567+7370A>G		intron_variant	Intron 22 of 23			ENSP00000498895.1

Frequencies

GnomAD3 genomes AF: 0.291 AC: 44197 AN: 152026 Hom.: 7715 Cov.: 33

Gnomad AFR AF: 0.0883

Gnomad AMI AF: 0.421

Gnomad AMR AF: 0.395

Gnomad ASJ AF: 0.320

Gnomad EAS AF: 0.468

Gnomad SAS AF: 0.344

Gnomad FIN AF: 0.325

Gnomad MID AF: 0.256

Gnomad NFE AF: 0.364

Gnomad OTH AF: 0.317

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

GnomAD4 genome AF: 0.291 AC: 44200 AN: 152142 Hom.: 7714 Cov.: 33 AF XY: 0.294 AC XY: 21839 AN XY: 74364

African (AFR) AF: 0.0883 AC: 3669 AN: 41550

American (AMR) AF: 0.395 AC: 6041 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.320 AC: 1110 AN: 3470

East Asian (EAS) AF: 0.469 AC: 2420 AN: 5162

South Asian (SAS) AF: 0.343 AC: 1653 AN: 4816

European-Finnish (FIN) AF: 0.325 AC: 3438 AN: 10592

Middle Eastern (MID) AF: 0.245 AC: 72 AN: 294

European-Non Finnish (NFE) AF: 0.364 AC: 24750 AN: 67950

Other (OTH) AF: 0.315 AC: 663 AN: 2108

Alfa AF: 0.342 Hom.: 36998

Bravo AF: 0.289

Asia WGS AF: 0.383 AC: 1332 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	6.2
DANN	Benign	0.71
PhyloP100		0.21
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
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: rs12699477; hg19: chr7-1968953;