1-11026275-A-G

Position:

• chr1-11026275-A-G

Variant summary

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

The ENST00000700088.1(MASP2):​c.1396+475T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.64 in 152,190 control chromosomes in the GnomAD database, including 35,529 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 0.64 (35529 hom., cov: 34)
  • Exomes 𝑓: 0.73 (11 hom.)
  • Failed GnomAD Quality Control
• Consequence: MASP2 ENST00000700088.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.33

Genes affected

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]

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.806 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TARDBP	XR_007058560.1	n.2508+610A>G		intron_variant, non_coding_transcript_variant
TARDBP	XR_007058562.1	n.2393+1067A>G		intron_variant, non_coding_transcript_variant
TARDBP	XR_007058563.1	n.2236+610A>G		intron_variant, non_coding_transcript_variant
TARDBP	XR_007058564.1	n.2121+1067A>G		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TARDBP	ENST00000612542.1	c.*22+1067A>G		intron_variant		5		ENSP00000478249
MASP2	ENST00000700088.1	c.1396+475T>C		intron_variant				ENSP00000514787
TARDBP	ENST00000611136.4	c.*180+1067A>G		intron_variant, NMD_transcript_variant		5		ENSP00000481737

Frequencies

GnomAD3 genomes AF: 0.640 AC: 97357 AN: 152072 Hom.: 35518 Cov.: 34

Gnomad AFR AF: 0.260

Gnomad AMI AF: 0.868

Gnomad AMR AF: 0.727

Gnomad ASJ AF: 0.690

Gnomad EAS AF: 0.658

Gnomad SAS AF: 0.693

Gnomad FIN AF: 0.816

Gnomad MID AF: 0.722

Gnomad NFE AF: 0.812

Gnomad OTH AF: 0.683

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.727 AC: 32 AN: 44 Hom.: 11 Cov.: 0 AF XY: 0.750 AC XY: 21 AN XY: 28

Gnomad4 FIN exome AF: 0.700

Gnomad4 NFE exome AF: 1.00

Gnomad4 OTH exome AF: 1.00

GnomAD4 genome AF: 0.640 AC: 97398 AN: 152190 Hom.: 35529 Cov.: 34 AF XY: 0.641 AC XY: 47697 AN XY: 74416

Gnomad4 AFR AF: 0.260

Gnomad4 AMR AF: 0.727

Gnomad4 ASJ AF: 0.690

Gnomad4 EAS AF: 0.658

Gnomad4 SAS AF: 0.693

Gnomad4 FIN AF: 0.816

Gnomad4 NFE AF: 0.812

Gnomad4 OTH AF: 0.685

Alfa AF: 0.776 Hom.: 46990

Bravo AF: 0.619

Asia WGS AF: 0.652 AC: 2269 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	0.20
DANN	Benign	0.48

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: rs2273347; hg19: chr1-11086332;