rs4721184

Positions:

• chr7-1911148-T-C
• chr7-1911148-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.1808-12758A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.303 in 152,012 control chromosomes in the GnomAD database, including 8,352 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 (8352 hom., cov: 32)
• Consequence: MAD1L1 NM_001013836.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.190

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 = 0.45 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MAD1L1	NM_001013836.2	c.1808-12758A>G		intron_variant		ENST00000265854.12

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MAD1L1	ENST00000265854.12	c.1808-12758A>G		intron_variant		1	NM_001013836.2	P1

Frequencies

GnomAD3 genomes AF: 0.303 AC: 46087 AN: 151894 Hom.: 8343 Cov.: 32

Gnomad AFR AF: 0.0920

Gnomad AMI AF: 0.439

Gnomad AMR AF: 0.413

Gnomad ASJ AF: 0.360

Gnomad EAS AF: 0.464

Gnomad SAS AF: 0.347

Gnomad FIN AF: 0.331

Gnomad MID AF: 0.278

Gnomad NFE AF: 0.382

Gnomad OTH AF: 0.338

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

GnomAD4 genome AF: 0.303 AC: 46099 AN: 152012 Hom.: 8352 Cov.: 32 AF XY: 0.305 AC XY: 22690 AN XY: 74284

Gnomad4 AFR AF: 0.0919

Gnomad4 AMR AF: 0.413

Gnomad4 ASJ AF: 0.360

Gnomad4 EAS AF: 0.465

Gnomad4 SAS AF: 0.347

Gnomad4 FIN AF: 0.331

Gnomad4 NFE AF: 0.382

Gnomad4 OTH AF: 0.342

Alfa AF: 0.337 Hom.: 4082

Bravo AF: 0.303

Asia WGS AF: 0.380 AC: 1319 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	3.8
DANN	Benign	0.80

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: rs4721184; hg19: chr7-1950784;