rs3757440

Variant names:

• chr7-2233301-A-G
• rs3757440
• ENST00000651235.1:n.*2121-331T>C

Your query was ambiguous. Multiple possible variants found:

• chr7-2233301-A-G
• chr7-2233301-A-T

Variant summary

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

The ENST00000651235.1(ENSG00000286192):​n.*2121-331T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.347 in 152,226 control chromosomes in the GnomAD database, including 9,399 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 0.35 (9393 hom., cov: 33)
  • Exomes 𝑓: 0.43 (6 hom.)
• Consequence: ENSG00000286192 ENST00000651235.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.215

Genes affected

ENSG00000286192 (HGNC:):

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 = 0.497 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ENSG00000286192	ENST00000651235.1	n.*2121-331T>C		intron_variant	Intron 4 of 23			ENSP00000498895.1
MAD1L1	ENST00000406869.5	c.-616T>C		upstream_gene_variant		1		ENSP00000385334.1

Frequencies

GnomAD3 genomes AF: 0.347 AC: 52719 AN: 152048 Hom.: 9388 Cov.: 33

Gnomad AFR AF: 0.328

Gnomad AMI AF: 0.221

Gnomad AMR AF: 0.385

Gnomad ASJ AF: 0.262

Gnomad EAS AF: 0.512

Gnomad SAS AF: 0.331

Gnomad FIN AF: 0.276

Gnomad MID AF: 0.199

Gnomad NFE AF: 0.355

Gnomad OTH AF: 0.357

GnomAD4 exome AF: 0.433 AC: 26 AN: 60 Hom.: 6 AF XY: 0.413 AC XY: 19 AN XY: 46

Gnomad4 SAS exome AF: 0.750

Gnomad4 FIN exome AF: 0.500

Gnomad4 NFE exome AF: 0.421

Gnomad4 OTH exome AF: 0.300

GnomAD4 genome AF: 0.347 AC: 52739 AN: 152166 Hom.: 9393 Cov.: 33 AF XY: 0.346 AC XY: 25726 AN XY: 74382

Gnomad4 AFR AF: 0.328

Gnomad4 AMR AF: 0.385

Gnomad4 ASJ AF: 0.262

Gnomad4 EAS AF: 0.513

Gnomad4 SAS AF: 0.331

Gnomad4 FIN AF: 0.276

Gnomad4 NFE AF: 0.355

Gnomad4 OTH AF: 0.355

Alfa AF: 0.356 Hom.: 893

Bravo AF: 0.358

Asia WGS AF: 0.439 AC: 1525 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	12
DANN	Benign	0.69

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs3757440; hg19: chr7-2272936;