rs1782455

Variant names:

• chr1-11027467-G-A
• rs1782455
• NM_006610.4:c.1479C>T

Your query was ambiguous. Multiple possible variants found:

• chr1-11027467-G-A
• chr1-11027467-G-C
• chr1-11027467-G-T

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BA1

The NM_006610.4(MASP2):​c.1479C>T​(p.Ser493Ser) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.806 in 1,613,586 control chromosomes in the GnomAD database, including 534,265 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.69 (39519 hom., cov: 31)
  • Exomes 𝑓: 0.82 (494746 hom.)
• Consequence: MASP2 NM_006610.4 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:5
• Conservation: PhyloP100: -1.31
• Publications: 36 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: ClinGen, Labcorp Genetics (formerly Invitae), Genomics England PanelApp, Ambry Genetics
• 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 -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).
• BP6: Variant 1-11027467-G-A is Benign according to our data. Variant chr1-11027467-G-A is described in ClinVar as Benign. ClinVar VariationId is 291781.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-1.31 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.842 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MASP2	NM_006610.4	c.1479C>T	p.Ser493Ser	synonymous_variant	Exon 11 of 11	ENST00000400897.8	NP_006601.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MASP2	ENST00000400897.8	c.1479C>T	p.Ser493Ser	synonymous_variant	Exon 11 of 11	1	NM_006610.4	ENSP00000383690.3

Frequencies

GnomAD3 genomes AF: 0.689 AC: 104692 AN: 151866 Hom.: 39509 Cov.: 31

Gnomad AFR AF: 0.352

Gnomad AMI AF: 0.890

Gnomad AMR AF: 0.758

Gnomad ASJ AF: 0.725

Gnomad EAS AF: 0.864

Gnomad SAS AF: 0.793

Gnomad FIN AF: 0.827

Gnomad MID AF: 0.769

Gnomad NFE AF: 0.831

Gnomad OTH AF: 0.737

GnomAD2 exomes AF: 0.793 AC: 199509 AN: 251474 AF XY: 0.800

Gnomad AFR exome AF: 0.339

Gnomad AMR exome AF: 0.825

Gnomad ASJ exome AF: 0.732

Gnomad EAS exome AF: 0.867

Gnomad FIN exome AF: 0.830

Gnomad NFE exome AF: 0.835

Gnomad OTH exome AF: 0.799

GnomAD4 exome AF: 0.818 AC: 1196308 AN: 1461602 Hom.: 494746 Cov.: 52 AF XY: 0.818 AC XY: 595118 AN XY: 727126

African (AFR) AF: 0.321 AC: 10759 AN: 33470

American (AMR) AF: 0.818 AC: 36603 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.733 AC: 19158 AN: 26134

East Asian (EAS) AF: 0.870 AC: 34540 AN: 39698

South Asian (SAS) AF: 0.790 AC: 68177 AN: 86250

European-Finnish (FIN) AF: 0.832 AC: 44433 AN: 53414

Middle Eastern (MID) AF: 0.755 AC: 4354 AN: 5768

European-Non Finnish (NFE) AF: 0.837 AC: 930281 AN: 1111754

Other (OTH) AF: 0.795 AC: 48003 AN: 60390

GnomAD4 genome AF: 0.689 AC: 104739 AN: 151984 Hom.: 39519 Cov.: 31 AF XY: 0.692 AC XY: 51388 AN XY: 74284

African (AFR) AF: 0.352 AC: 14555 AN: 41406

American (AMR) AF: 0.759 AC: 11569 AN: 15250

Ashkenazi Jewish (ASJ) AF: 0.725 AC: 2516 AN: 3470

East Asian (EAS) AF: 0.864 AC: 4463 AN: 5168

South Asian (SAS) AF: 0.793 AC: 3816 AN: 4812

European-Finnish (FIN) AF: 0.827 AC: 8740 AN: 10574

Middle Eastern (MID) AF: 0.772 AC: 227 AN: 294

European-Non Finnish (NFE) AF: 0.831 AC: 56483 AN: 67992

Other (OTH) AF: 0.740 AC: 1558 AN: 2106

Alfa AF: 0.772 Hom.: 77238

Bravo AF: 0.671

Asia WGS AF: 0.782 AC: 2718 AN: 3478

EpiCase AF: 0.825

EpiControl AF: 0.828

ClinVar

Significance: Benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:1

Mar 29, 2016

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Variant identified in a genome or exome case(s) and assessed due to predicted null impact of the variant or pathogenic assertions in the literature or databases. Disclaimer: This variant has not undergone full assessment. The following are preliminary notes: Frequency -

Immunodeficiency due to MASP-2 deficiency Benign:1

Jun 14, 2016

Illumina Laboratory Services, Illumina

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Amyotrophic Lateral Sclerosis, Dominant Benign:1

Jun 14, 2016

Illumina Laboratory Services, Illumina

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Frontotemporal dementia Benign:1

Jun 14, 2016

Illumina Laboratory Services, Illumina

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

not provided Benign:1

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	1.7
DANN	Benign	0.47
PhyloP100		-1.3
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: rs1782455; hg19: chr1-11087524; COSMIC: COSV53571447; COSMIC: COSV53571447;