7-1936920-G-A

Variant names:

• chr7-1936920-G-A
• rs2280550
• NM_001013836.2:c.1597-23C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_003550.3(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_003550.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.31
• Publications: 18 publications found

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]

MAD1L1 Gene-Disease associations (from GenCC):

• mosaic variegated aneuploidy syndrome 7 with inflammation and tumor predisposition

  Inheritance: AR Classification: LIMITED Submitted by: Ambry Genetics
• familial prostate carcinoma

  Inheritance: Unknown Classification: LIMITED Submitted by: Labcorp Genetics (formerly Invitae)

ENSG00000286192 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_003550.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MAD1L1	NM_001013836.2	MANE Select	c.1597-23C>T		intron	N/A	NP_001013858.1
	MAD1L1	NM_001013837.2		c.1597-23C>T		intron	N/A	NP_001013859.1
	MAD1L1	NM_001304523.2		c.1597-23C>T		intron	N/A	NP_001291452.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MAD1L1	ENST00000265854.12	TSL:1 MANE Select	c.1597-23C>T		intron	N/A	ENSP00000265854.7
	MAD1L1	ENST00000406869.5	TSL:1	c.1597-23C>T		intron	N/A	ENSP00000385334.1
	ENSG00000286192	ENST00000651235.1		n.*4357-23C>T		intron	N/A	ENSP00000498895.1

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

GnomAD2 exomes AF: 0.358 AC: 64155 AN: 179374 AF XY: 0.357

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 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

African (AFR) AF: 0.0744 AC: 2420 AN: 32528

American (AMR) AF: 0.441 AC: 16668 AN: 37758

Ashkenazi Jewish (ASJ) AF: 0.303 AC: 7469 AN: 24670

East Asian (EAS) AF: 0.448 AC: 16783 AN: 37482

South Asian (SAS) AF: 0.335 AC: 26680 AN: 79678

European-Finnish (FIN) AF: 0.308 AC: 15046 AN: 48836

Middle Eastern (MID) AF: 0.308 AC: 1741 AN: 5660

European-Non Finnish (NFE) AF: 0.388 AC: 417532 AN: 1077428

Other (OTH) AF: 0.369 AC: 21441 AN: 58084

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

African (AFR) AF: 0.0917 AC: 3812 AN: 41550

American (AMR) AF: 0.411 AC: 6283 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.305 AC: 1058 AN: 3472

East Asian (EAS) AF: 0.470 AC: 2429 AN: 5172

South Asian (SAS) AF: 0.343 AC: 1652 AN: 4810

European-Finnish (FIN) AF: 0.300 AC: 3182 AN: 10590

Middle Eastern (MID) AF: 0.245 AC: 72 AN: 294

European-Non Finnish (NFE) AF: 0.370 AC: 25126 AN: 67972

Other (OTH) AF: 0.328 AC: 692 AN: 2110

Alfa AF: 0.355 Hom.: 17863

Bravo AF: 0.296

Asia WGS AF: 0.383 AC: 1332 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	9.4
DANN	Benign	0.71
PhyloP100		3.3
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs2280550; hg19: chr7-1976556; COSMIC: COSV56229699;