rs4721190

Positions:

• chr7-1915096-G-A
• chr7-1915096-G-T

Variant summary

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

The NM_001013836.2(MAD1L1):​c.1808-16706C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.331 in 152,110 control chromosomes in the GnomAD database, including 10,043 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 0.33 (10043 hom., cov: 32)
• Consequence: MAD1L1 NM_001013836.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.467

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=-1.0).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.469 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MAD1L1	NM_001013836.2	c.1808-16706C>T		intron_variant		ENST00000265854.12	NP_001013858.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MAD1L1	ENST00000265854.12	c.1808-16706C>T		intron_variant		1	NM_001013836.2	ENSP00000265854	P1

Frequencies

GnomAD3 genomes AF: 0.331 AC: 50362 AN: 151992 Hom.: 10030 Cov.: 32

Gnomad AFR AF: 0.0992

Gnomad AMI AF: 0.568

Gnomad AMR AF: 0.477

Gnomad ASJ AF: 0.382

Gnomad EAS AF: 0.464

Gnomad SAS AF: 0.411

Gnomad FIN AF: 0.328

Gnomad MID AF: 0.322

Gnomad NFE AF: 0.418

Gnomad OTH AF: 0.367

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

GnomAD4 genome AF: 0.331 AC: 50379 AN: 152110 Hom.: 10043 Cov.: 32 AF XY: 0.332 AC XY: 24716 AN XY: 74348

Gnomad4 AFR AF: 0.0991

Gnomad4 AMR AF: 0.478

Gnomad4 ASJ AF: 0.382

Gnomad4 EAS AF: 0.465

Gnomad4 SAS AF: 0.410

Gnomad4 FIN AF: 0.328

Gnomad4 NFE AF: 0.418

Gnomad4 OTH AF: 0.364

Alfa AF: 0.288 Hom.: 1077

Bravo AF: 0.337

Asia WGS AF: 0.404 AC: 1404 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	1.7
DANN	Benign	0.29

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: rs4721190; hg19: chr7-1954732;