7-1936920-G-A

Position:

• chr7-1936920-G-A

Variant summary

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

The NM_001013836.2(MAD1L1):​c.1597-23C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.367 in 1,554,304 control chromosomes in the GnomAD database, including 109,658 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 (7864 hom., cov: 34)
  • Exomes 𝑓: 0.37 (101794 hom.)
• Consequence: MAD1L1 NM_001013836.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.31

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=-0.8).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.454 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MAD1L1	NM_001013836.2	c.1597-23C>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.1597-23C>T		intron_variant		1	NM_001013836.2	ENSP00000265854	P1

Frequencies

GnomAD3 genomes AF: 0.294 AC: 44693 AN: 152062 Hom.: 7864 Cov.: 34

Gnomad AFR AF: 0.0918

Gnomad AMI AF: 0.429

Gnomad AMR AF: 0.411

Gnomad ASJ AF: 0.305

Gnomad EAS AF: 0.469

Gnomad SAS AF: 0.344

Gnomad FIN AF: 0.300

Gnomad MID AF: 0.256

Gnomad NFE AF: 0.370

Gnomad OTH AF: 0.331

GnomAD3 exomes AF: 0.358 AC: 64155 AN: 179374 Hom.: 12147 AF XY: 0.357 AC XY: 34279 AN XY: 96022

Gnomad AFR exome AF: 0.0805

Gnomad AMR exome AF: 0.450

Gnomad ASJ exome AF: 0.303

Gnomad EAS exome AF: 0.479

Gnomad SAS exome AF: 0.338

Gnomad FIN exome AF: 0.308

Gnomad NFE exome AF: 0.367

Gnomad OTH exome AF: 0.349

GnomAD4 exome AF: 0.375 AC: 525780 AN: 1402124 Hom.: 101794 Cov.: 32 AF XY: 0.374 AC XY: 258360 AN XY: 690796

Gnomad4 AFR exome AF: 0.0744

Gnomad4 AMR exome AF: 0.441

Gnomad4 ASJ exome AF: 0.303

Gnomad4 EAS exome AF: 0.448

Gnomad4 SAS exome AF: 0.335

Gnomad4 FIN exome AF: 0.308

Gnomad4 NFE exome AF: 0.388

Gnomad4 OTH exome AF: 0.369

GnomAD4 genome AF: 0.294 AC: 44697 AN: 152180 Hom.: 7864 Cov.: 34 AF XY: 0.296 AC XY: 22013 AN XY: 74408

Gnomad4 AFR AF: 0.0917

Gnomad4 AMR AF: 0.411

Gnomad4 ASJ AF: 0.305

Gnomad4 EAS AF: 0.470

Gnomad4 SAS AF: 0.343

Gnomad4 FIN AF: 0.300

Gnomad4 NFE AF: 0.370

Gnomad4 OTH AF: 0.328

Alfa AF: 0.364 Hom.: 12028

Bravo AF: 0.296

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	-0.80
CADD	Benign	9.4
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: rs2280550; hg19: chr7-1976556; COSMIC: COSV56229699;