7-1846899-G-C

Position:

• chr7-1846899-G-C

Variant summary

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

The NM_001013836.2(MAD1L1):​c.1999-30671C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.345 in 273,910 control chromosomes in the GnomAD database, including 16,938 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 0.36 (10227 hom., cov: 34)
  • Exomes 𝑓: 0.32 (6711 hom.)
• Consequence: MAD1L1 NM_001013836.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.18

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]

(HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.66).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.437 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MAD1L1	NM_001013836.2	c.1999-30671C>G		intron_variant		ENST00000265854.12
LOC100127955	XR_108730.5	n.203-349G>C		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MAD1L1	ENST00000265854.12	c.1999-30671C>G		intron_variant		1	NM_001013836.2	P1
	ENST00000402221.4	n.284-349G>C		intron_variant, non_coding_transcript_variant		2

Frequencies

GnomAD3 genomes AF: 0.364 AC: 55288 AN: 152070 Hom.: 10217 Cov.: 34

Gnomad AFR AF: 0.386

Gnomad AMI AF: 0.418

Gnomad AMR AF: 0.446

Gnomad ASJ AF: 0.319

Gnomad EAS AF: 0.447

Gnomad SAS AF: 0.417

Gnomad FIN AF: 0.270

Gnomad MID AF: 0.294

Gnomad NFE AF: 0.337

Gnomad OTH AF: 0.379

GnomAD4 exome AF: 0.321 AC: 39051 AN: 121722 Hom.: 6711 Cov.: 0 AF XY: 0.327 AC XY: 21388 AN XY: 65484

Gnomad4 AFR exome AF: 0.336

Gnomad4 AMR exome AF: 0.438

Gnomad4 ASJ exome AF: 0.266

Gnomad4 EAS exome AF: 0.396

Gnomad4 SAS exome AF: 0.363

Gnomad4 FIN exome AF: 0.253

Gnomad4 NFE exome AF: 0.307

Gnomad4 OTH exome AF: 0.307

GnomAD4 genome AF: 0.363 AC: 55311 AN: 152188 Hom.: 10227 Cov.: 34 AF XY: 0.364 AC XY: 27082 AN XY: 74414

Gnomad4 AFR AF: 0.386

Gnomad4 AMR AF: 0.445

Gnomad4 ASJ AF: 0.319

Gnomad4 EAS AF: 0.448

Gnomad4 SAS AF: 0.417

Gnomad4 FIN AF: 0.270

Gnomad4 NFE AF: 0.337

Gnomad4 OTH AF: 0.376

Alfa AF: 0.332 Hom.: 1046

Bravo AF: 0.382

Asia WGS AF: 0.421 AC: 1461 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.66
CADD	Benign	14
DANN	Benign	0.46

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: rs6952808; hg19: chr7-1886535;