1-11026382-C-T

Position:

• chr1-11026382-C-T

Variant summary

Our verdict is Benign. Variant got -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

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]

ACMG classification

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TARDBP	XR_007058560.1	n.2508+717C>T		intron_variant, non_coding_transcript_variant
TARDBP	XR_007058562.1	n.2393+1174C>T		intron_variant, non_coding_transcript_variant
TARDBP	XR_007058563.1	n.2236+717C>T		intron_variant, non_coding_transcript_variant
TARDBP	XR_007058564.1	n.2121+1174C>T		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MASP2	ENST00000700091.1	c.*503G>A		3_prime_UTR_variant	9/9			ENSP00000514790
MASP2	ENST00000700092.1	c.*503G>A		3_prime_UTR_variant	11/11			ENSP00000514791
MASP2	ENST00000700093.1	c.*503G>A		3_prime_UTR_variant	11/11			ENSP00000514792

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

Gnomad4 AFR exome AF: 0.750

Gnomad4 AMR exome AF: 0.833

Gnomad4 ASJ exome AF: 0.500

Gnomad4 SAS exome AF: 1.00

Gnomad4 FIN exome AF: 0.591

Gnomad4 NFE exome AF: 0.772

Gnomad4 OTH exome AF: 0.750

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

Gnomad4 AFR AF: 0.813

Gnomad4 AMR AF: 0.813

Gnomad4 ASJ AF: 0.734

Gnomad4 EAS AF: 0.863

Gnomad4 SAS AF: 0.795

Gnomad4 FIN AF: 0.819

Gnomad4 NFE AF: 0.824

Gnomad4 OTH AF: 0.839

Alfa AF: 0.823 Hom.: 15753

Bravo AF: 0.820

Asia WGS AF: 0.817 AC: 2840 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

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

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