rs3800913

Variant names:

• chr7-2123602-A-G
• rs3800913
• NM_001013836.2:c.1073+25550T>C

Variant summary

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

The NM_001013836.2(MAD1L1):​c.1073+25550T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.343 in 152,100 control chromosomes in the GnomAD database, including 10,091 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 (10091 hom., cov: 33)
• Consequence: MAD1L1 NM_001013836.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -3.49

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]

ENSG00000286192 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.97).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.498 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MAD1L1	NM_001013836.2	c.1073+25550T>C		intron_variant	Intron 11 of 18	ENST00000265854.12	NP_001013858.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MAD1L1	ENST00000265854.12	c.1073+25550T>C		intron_variant	Intron 11 of 18	1	NM_001013836.2	ENSP00000265854.7
ENSG00000286192	ENST00000651235.1	n.*3833+25494T>C		intron_variant	Intron 16 of 23			ENSP00000498895.1

Frequencies

GnomAD3 genomes AF: 0.343 AC: 52112 AN: 151982 Hom.: 10092 Cov.: 33

Gnomad AFR AF: 0.155

Gnomad AMI AF: 0.324

Gnomad AMR AF: 0.452

Gnomad ASJ AF: 0.324

Gnomad EAS AF: 0.514

Gnomad SAS AF: 0.421

Gnomad FIN AF: 0.375

Gnomad MID AF: 0.282

Gnomad NFE AF: 0.410

Gnomad OTH AF: 0.372

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

GnomAD4 genome AF: 0.343 AC: 52118 AN: 152100 Hom.: 10091 Cov.: 33 AF XY: 0.346 AC XY: 25754 AN XY: 74364

Gnomad4 AFR AF: 0.155

Gnomad4 AMR AF: 0.453

Gnomad4 ASJ AF: 0.324

Gnomad4 EAS AF: 0.514

Gnomad4 SAS AF: 0.419

Gnomad4 FIN AF: 0.375

Gnomad4 NFE AF: 0.410

Gnomad4 OTH AF: 0.371

Alfa AF: 0.396 Hom.: 5865

Bravo AF: 0.343

Asia WGS AF: 0.436 AC: 1517 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	0.21
DANN	Benign	0.14

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: rs3800913; hg19: chr7-2163237; COSMIC: COSV56230169;