7-1929317-T-C

Position:

• chr7-1929317-T-C

Variant summary

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

The NM_001013836.2(MAD1L1):​c.1807+7370A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.291 in 152,142 control chromosomes in the GnomAD database, including 7,714 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 (7714 hom., cov: 33)
• Consequence: MAD1L1 NM_001013836.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.211

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 = 0.453 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MAD1L1	NM_001013836.2	c.1807+7370A>G		intron_variant		ENST00000265854.12	NP_001013858.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MAD1L1	ENST00000265854.12	c.1807+7370A>G		intron_variant		1	NM_001013836.2	ENSP00000265854	P1

Frequencies

GnomAD3 genomes AF: 0.291 AC: 44197 AN: 152026 Hom.: 7715 Cov.: 33

Gnomad AFR AF: 0.0883

Gnomad AMI AF: 0.421

Gnomad AMR AF: 0.395

Gnomad ASJ AF: 0.320

Gnomad EAS AF: 0.468

Gnomad SAS AF: 0.344

Gnomad FIN AF: 0.325

Gnomad MID AF: 0.256

Gnomad NFE AF: 0.364

Gnomad OTH AF: 0.317

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

GnomAD4 genome AF: 0.291 AC: 44200 AN: 152142 Hom.: 7714 Cov.: 33 AF XY: 0.294 AC XY: 21839 AN XY: 74364

Gnomad4 AFR AF: 0.0883

Gnomad4 AMR AF: 0.395

Gnomad4 ASJ AF: 0.320

Gnomad4 EAS AF: 0.469

Gnomad4 SAS AF: 0.343

Gnomad4 FIN AF: 0.325

Gnomad4 NFE AF: 0.364

Gnomad4 OTH AF: 0.315

Alfa AF: 0.353 Hom.: 14360

Bravo AF: 0.289

Asia WGS AF: 0.383 AC: 1332 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	6.2
DANN	Benign	0.71
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: rs12699477; hg19: chr7-1968953;