chr1-11026382-C-T

Variant names:

• chr1-11026382-C-T
• rs2261695
• ENST00000700092.1:c.*503G>A

Variant summary

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

The ENST00000700092.1(MASP2):​c.*503G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.818 in 152,362 control chromosomes in the GnomAD database, including 51,100 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 0.82 (51053 hom., cov: 33)
  • Exomes 𝑓: 0.75 (47 hom.)
• Consequence: MASP2 ENST00000700092.1 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.133
• Publications: 10 publications found

Genes affected

MASP2 (HGNC:6902): (MBL associated serine protease 2) This gene encodes a member of the peptidase S1 family of serine proteases. The encoded preproprotein is proteolytically processed to generate A and B chains that heterodimerize to form the mature protease. This protease cleaves complement components C2 and C4 in order to generate C3 convertase in the lectin pathway of the complement system. The encoded protease also plays a role in the coagulation cascade through cleavage of prothrombin to form thrombin. Myocardial infarction and acute stroke patients exhibit reduced serum concentrations of the encoded protein. Alternative splicing results in multiple transcript variants, at least one of which encodes an isoform that is proteolytically processed. [provided by RefSeq, Feb 2016]

TARDBP (HGNC:11571): (TAR DNA binding protein) HIV-1, the causative agent of acquired immunodeficiency syndrome (AIDS), contains an RNA genome that produces a chromosomally integrated DNA during the replicative cycle. Activation of HIV-1 gene expression by the transactivator Tat is dependent on an RNA regulatory element (TAR) located downstream of the transcription initiation site. The protein encoded by this gene is a transcriptional repressor that binds to chromosomally integrated TAR DNA and represses HIV-1 transcription. In addition, this protein regulates alternate splicing of the CFTR gene. A similar pseudogene is present on chromosome 20. [provided by RefSeq, Jul 2008]

TARDBP Gene-Disease associations (from GenCC):

• amyotrophic lateral sclerosis type 10

  Inheritance: AD Classification: DEFINITIVE, STRONG Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics, ClinGen, Genomics England PanelApp
• amyotrophic lateral sclerosis

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
• frontotemporal dementia with motor neuron disease

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
• inclusion body myositis

  Inheritance: AD Classification: LIMITED Submitted by: Broad Center for Mendelian Genomics

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.841 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000700092.1. 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
	MASP2	NM_006610.4	MANE Select	c.*503G>A		downstream_gene	N/A	NP_006601.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MASP2	ENST00000700092.1		c.*503G>A		3_prime_UTR	Exon 11 of 11	ENSP00000514791.1	A0A8V8TQL2
	MASP2	ENST00000700093.1		c.*503G>A		3_prime_UTR	Exon 11 of 11	ENSP00000514792.1	A0A8V8TPU1
	MASP2	ENST00000700091.1		c.*503G>A		3_prime_UTR	Exon 9 of 9	ENSP00000514790.1	A0A8V8TPN3

Frequencies

GnomAD3 genomes AF: 0.818 AC: 124468 AN: 152082 Hom.: 51007 Cov.: 33

Gnomad AFR AF: 0.813

Gnomad AMI AF: 0.888

Gnomad AMR AF: 0.813

Gnomad ASJ AF: 0.734

Gnomad EAS AF: 0.863

Gnomad SAS AF: 0.794

Gnomad FIN AF: 0.819

Gnomad MID AF: 0.793

Gnomad NFE AF: 0.824

Gnomad OTH AF: 0.837

GnomAD4 exome AF: 0.747 AC: 121 AN: 162 Hom.: 47 Cov.: 0 AF XY: 0.762 AC XY: 61 AN XY: 80

African (AFR) AF: 0.750 AC: 6 AN: 8

American (AMR) AF: 0.833 AC: 5 AN: 6

Ashkenazi Jewish (ASJ) AF: 0.500 AC: 1 AN: 2

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AF: 1.00 AC: 2 AN: 2

European-Finnish (FIN) AF: 0.591 AC: 13 AN: 22

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.772 AC: 88 AN: 114

Other (OTH) AF: 0.750 AC: 6 AN: 8

GnomAD4 genome AF: 0.818 AC: 124575 AN: 152200 Hom.: 51053 Cov.: 33 AF XY: 0.817 AC XY: 60762 AN XY: 74412

African (AFR) AF: 0.813 AC: 33759 AN: 41522

American (AMR) AF: 0.813 AC: 12415 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.734 AC: 2546 AN: 3470

East Asian (EAS) AF: 0.863 AC: 4473 AN: 5186

South Asian (SAS) AF: 0.795 AC: 3835 AN: 4826

European-Finnish (FIN) AF: 0.819 AC: 8688 AN: 10610

Middle Eastern (MID) AF: 0.795 AC: 232 AN: 292

European-Non Finnish (NFE) AF: 0.824 AC: 56045 AN: 67998

Other (OTH) AF: 0.839 AC: 1772 AN: 2112

Alfa AF: 0.823 Hom.: 19698

Bravo AF: 0.820

Asia WGS AF: 0.817 AC: 2840 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	1.2
DANN	Benign	0.58
PhyloP100		-0.13

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: rs2261695; hg19: chr1-11086439; COSMIC: COSV53570731; COSMIC: COSV53570731;