rs4721295

Positions:

• chr7-1997034-T-G

Variant summary

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

The NM_001013836.2(MAD1L1):​c.1416+5031A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.336 in 152,052 control chromosomes in the GnomAD database, including 9,557 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 0.34 (9557 hom., cov: 33)
• Consequence: MAD1L1 NM_001013836.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.520

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=-0.82).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.548 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MAD1L1	NM_001013836.2	c.1416+5031A>C		intron_variant		ENST00000265854.12

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MAD1L1	ENST00000265854.12	c.1416+5031A>C		intron_variant		1	NM_001013836.2	P1

Frequencies

GnomAD3 genomes AF: 0.336 AC: 51098 AN: 151934 Hom.: 9555 Cov.: 33

Gnomad AFR AF: 0.176

Gnomad AMI AF: 0.195

Gnomad AMR AF: 0.448

Gnomad ASJ AF: 0.389

Gnomad EAS AF: 0.564

Gnomad SAS AF: 0.336

Gnomad FIN AF: 0.335

Gnomad MID AF: 0.247

Gnomad NFE AF: 0.390

Gnomad OTH AF: 0.370

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

GnomAD4 genome AF: 0.336 AC: 51098 AN: 152052 Hom.: 9557 Cov.: 33 AF XY: 0.337 AC XY: 25065 AN XY: 74320

Gnomad4 AFR AF: 0.175

Gnomad4 AMR AF: 0.448

Gnomad4 ASJ AF: 0.389

Gnomad4 EAS AF: 0.565

Gnomad4 SAS AF: 0.336

Gnomad4 FIN AF: 0.335

Gnomad4 NFE AF: 0.390

Gnomad4 OTH AF: 0.368

Alfa AF: 0.360 Hom.: 1812

Bravo AF: 0.339

Asia WGS AF: 0.428 AC: 1482 AN: 3470

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	0.88
DANN	Benign	0.33

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: rs4721295; hg19: chr7-2036669;