7-1843278-G-T

Position:

• chr7-1843278-G-T

Variant summary

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

The NM_001013836.2(MAD1L1):​c.1999-27050C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0779 in 152,214 control chromosomes in the GnomAD database, including 655 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 0.078 (655 hom., cov: 33)
• Consequence: MAD1L1 NM_001013836.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.413

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=-0.89).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.258 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MAD1L1	NM_001013836.2	c.1999-27050C>A		intron_variant		ENST00000265854.12	NP_001013858.1
LOC100127955	XR_108730.5	n.203-3970G>T		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MAD1L1	ENST00000265854.12	c.1999-27050C>A		intron_variant		1	NM_001013836.2	ENSP00000265854	P1
	ENST00000402221.4	n.284-3970G>T		intron_variant, non_coding_transcript_variant		2

Frequencies

GnomAD3 genomes AF: 0.0779 AC: 11850 AN: 152096 Hom.: 659 Cov.: 33

Gnomad AFR AF: 0.0186

Gnomad AMI AF: 0.0363

Gnomad AMR AF: 0.103

Gnomad ASJ AF: 0.0404

Gnomad EAS AF: 0.269

Gnomad SAS AF: 0.0967

Gnomad FIN AF: 0.0846

Gnomad MID AF: 0.0350

Gnomad NFE AF: 0.0943

Gnomad OTH AF: 0.0746

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

GnomAD4 genome AF: 0.0779 AC: 11852 AN: 152214 Hom.: 655 Cov.: 33 AF XY: 0.0784 AC XY: 5838 AN XY: 74422

Gnomad4 AFR AF: 0.0186

Gnomad4 AMR AF: 0.103

Gnomad4 ASJ AF: 0.0404

Gnomad4 EAS AF: 0.270

Gnomad4 SAS AF: 0.0961

Gnomad4 FIN AF: 0.0846

Gnomad4 NFE AF: 0.0943

Gnomad4 OTH AF: 0.0743

Alfa AF: 0.0889 Hom.: 393

Bravo AF: 0.0771

Asia WGS AF: 0.155 AC: 539 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.44
DANN	Benign	0.50
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: rs11767177; hg19: chr7-1882914;