rs12537914

Positions:

• chr7-1908723-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001013836.2(MAD1L1):​c.1808-10333G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.301 in 152,018 control chromosomes in the GnomAD database, including 8,213 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 0.30 (8213 hom., cov: 32)
• Consequence: MAD1L1 NM_001013836.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.662

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.432 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MAD1L1	NM_001013836.2	c.1808-10333G>A		intron_variant		ENST00000265854.12

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MAD1L1	ENST00000265854.12	c.1808-10333G>A		intron_variant		1	NM_001013836.2	P1

Frequencies

GnomAD3 genomes AF: 0.301 AC: 45735 AN: 151900 Hom.: 8205 Cov.: 32

Gnomad AFR AF: 0.0916

Gnomad AMI AF: 0.440

Gnomad AMR AF: 0.410

Gnomad ASJ AF: 0.359

Gnomad EAS AF: 0.447

Gnomad SAS AF: 0.324

Gnomad FIN AF: 0.324

Gnomad MID AF: 0.275

Gnomad NFE AF: 0.382

Gnomad OTH AF: 0.335

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

GnomAD4 genome AF: 0.301 AC: 45747 AN: 152018 Hom.: 8213 Cov.: 32 AF XY: 0.302 AC XY: 22465 AN XY: 74310

Gnomad4 AFR AF: 0.0916

Gnomad4 AMR AF: 0.410

Gnomad4 ASJ AF: 0.359

Gnomad4 EAS AF: 0.448

Gnomad4 SAS AF: 0.323

Gnomad4 FIN AF: 0.324

Gnomad4 NFE AF: 0.382

Gnomad4 OTH AF: 0.339

Alfa AF: 0.332 Hom.: 1184

Bravo AF: 0.301

Asia WGS AF: 0.351 AC: 1218 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.89
DANN	Benign	0.82

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

Publications

LitVar

Other links and lift over

dbSNP: rs12537914; hg19: chr7-1948359;