rs4721190

Variant names:

• chr7-1915096-G-A
• rs4721190
• NM_001013836.2:c.1808-16706C>T

Your query was ambiguous. Multiple possible variants found:

• chr7-1915096-G-A
• chr7-1915096-G-T

Variant summary

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

The NM_001013836.2(MAD1L1):​c.1808-16706C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.331 in 152,110 control chromosomes in the GnomAD database, including 10,043 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 0.33 (10043 hom., cov: 32)
• Consequence: MAD1L1 NM_001013836.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.467
• Publications: 12 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=-1.0).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.469 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MAD1L1	NM_001013836.2	c.1808-16706C>T		intron_variant	Intron 17 of 18	ENST00000265854.12	NP_001013858.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MAD1L1	ENST00000265854.12	c.1808-16706C>T		intron_variant	Intron 17 of 18	1	NM_001013836.2	ENSP00000265854.7
ENSG00000286192	ENST00000651235.1	n.*4568-16706C>T		intron_variant	Intron 22 of 23			ENSP00000498895.1

Frequencies

GnomAD3 genomes AF: 0.331 AC: 50362 AN: 151992 Hom.: 10030 Cov.: 32

Gnomad AFR AF: 0.0992

Gnomad AMI AF: 0.568

Gnomad AMR AF: 0.477

Gnomad ASJ AF: 0.382

Gnomad EAS AF: 0.464

Gnomad SAS AF: 0.411

Gnomad FIN AF: 0.328

Gnomad MID AF: 0.322

Gnomad NFE AF: 0.418

Gnomad OTH AF: 0.367

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

GnomAD4 genome AF: 0.331 AC: 50379 AN: 152110 Hom.: 10043 Cov.: 32 AF XY: 0.332 AC XY: 24716 AN XY: 74348

African (AFR) AF: 0.0991 AC: 4115 AN: 41518

American (AMR) AF: 0.478 AC: 7288 AN: 15254

Ashkenazi Jewish (ASJ) AF: 0.382 AC: 1326 AN: 3470

East Asian (EAS) AF: 0.465 AC: 2398 AN: 5158

South Asian (SAS) AF: 0.410 AC: 1978 AN: 4822

European-Finnish (FIN) AF: 0.328 AC: 3473 AN: 10590

Middle Eastern (MID) AF: 0.308 AC: 90 AN: 292

European-Non Finnish (NFE) AF: 0.418 AC: 28426 AN: 67988

Other (OTH) AF: 0.364 AC: 768 AN: 2108

Alfa AF: 0.288 Hom.: 1077

Bravo AF: 0.337

Asia WGS AF: 0.404 AC: 1404 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	1.7
DANN	Benign	0.29
PhyloP100		-0.47
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: rs4721190; hg19: chr7-1954732;