7-2145267-C-T

Position:

• chr7-2145267-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.1073+3885G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.286 in 152,190 control chromosomes in the GnomAD database, including 7,550 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 0.29 (7550 hom., cov: 33)
• Consequence: MAD1L1 NM_001013836.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.52

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=-0.93).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.501 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MAD1L1	NM_001013836.2	c.1073+3885G>A		intron_variant		ENST00000265854.12

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MAD1L1	ENST00000265854.12	c.1073+3885G>A		intron_variant		1	NM_001013836.2	P1

Frequencies

GnomAD3 genomes AF: 0.286 AC: 43557 AN: 152072 Hom.: 7549 Cov.: 33

Gnomad AFR AF: 0.0880

Gnomad AMI AF: 0.190

Gnomad AMR AF: 0.398

Gnomad ASJ AF: 0.276

Gnomad EAS AF: 0.517

Gnomad SAS AF: 0.340

Gnomad FIN AF: 0.310

Gnomad MID AF: 0.212

Gnomad NFE AF: 0.358

Gnomad OTH AF: 0.322

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

GnomAD4 genome AF: 0.286 AC: 43558 AN: 152190 Hom.: 7550 Cov.: 33 AF XY: 0.290 AC XY: 21561 AN XY: 74382

Gnomad4 AFR AF: 0.0878

Gnomad4 AMR AF: 0.398

Gnomad4 ASJ AF: 0.276

Gnomad4 EAS AF: 0.518

Gnomad4 SAS AF: 0.340

Gnomad4 FIN AF: 0.310

Gnomad4 NFE AF: 0.358

Gnomad4 OTH AF: 0.321

Alfa AF: 0.318 Hom.: 2166

Bravo AF: 0.286

Asia WGS AF: 0.404 AC: 1402 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	1.1
DANN	Benign	0.44
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

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: rs3779003; hg19: chr7-2184902;