3-187221168-C-T

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_001879.6(MASP1):c.1810-34G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.286 in 1,521,678 control chromosomes in the GnomAD database, including 70,287 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.36 (10926 hom., cov: 32)
  • Exomes 𝑓: 0.28 (59361 hom.)
• Consequence: MASP1 NM_001879.6 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.424

Genes affected

MASP1 (HGNC:6901): (MBL associated serine protease 1) This gene encodes a serine protease that functions as a component of the lectin pathway of complement activation. The complement pathway plays an essential role in the innate and adaptive immune response. The encoded protein is synthesized as a zymogen and is activated when it complexes with the pathogen recognition molecules of lectin pathway, the mannose-binding lectin and the ficolins. This protein is not directly involved in complement activation but may play a role as an amplifier of complement activation by cleaving complement C2 or by activating another complement serine protease, MASP-2. The encoded protein is also able to cleave fibrinogen and factor XIII and may may be involved in coagulation. A splice variant of this gene which lacks the serine protease domain functions as an inhibitor of the complement pathway. Alternate splicing results in multiple transcript variants.[provided by RefSeq, Apr 2010]

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.94).
• BP6: Variant 3-187221168-C-T is Benign according to our data. Variant chr3-187221168-C-T is described in ClinVar as [Benign]. Clinvar id is 1222412.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.67 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MASP1	NM_001879.6	c.1810-34G>A		intron_variant		ENST00000337774.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MASP1	ENST00000337774.10	c.1810-34G>A		intron_variant		1	NM_001879.6	P1

Frequencies

GnomAD3 genomes AF: 0.355 AC: 53934 AN: 152012 Hom.: 10900 Cov.: 32

Gnomad AFR AF: 0.517

Gnomad AMI AF: 0.271

Gnomad AMR AF: 0.389

Gnomad ASJ AF: 0.285

Gnomad EAS AF: 0.689

Gnomad SAS AF: 0.365

Gnomad FIN AF: 0.240

Gnomad MID AF: 0.339

Gnomad NFE AF: 0.244

Gnomad OTH AF: 0.375

GnomAD3 exomes AF: 0.341 AC: 76259 AN: 223682 Hom.: 14539 AF XY: 0.333 AC XY: 39986 AN XY: 120230

Gnomad AFR exome AF: 0.523

Gnomad AMR exome AF: 0.420

Gnomad ASJ exome AF: 0.292

Gnomad EAS exome AF: 0.686

Gnomad SAS exome AF: 0.350

Gnomad FIN exome AF: 0.250

Gnomad NFE exome AF: 0.252

Gnomad OTH exome AF: 0.323

GnomAD4 exome AF: 0.279 AC: 381740 AN: 1369548 Hom.: 59361 Cov.: 20 AF XY: 0.279 AC XY: 191052 AN XY: 684678

Gnomad4 AFR exome AF: 0.531

Gnomad4 AMR exome AF: 0.413

Gnomad4 ASJ exome AF: 0.292

Gnomad4 EAS exome AF: 0.697

Gnomad4 SAS exome AF: 0.341

Gnomad4 FIN exome AF: 0.249

Gnomad4 NFE exome AF: 0.244

Gnomad4 OTH exome AF: 0.315

GnomAD4 genome AF: 0.355 AC: 54019 AN: 152130 Hom.: 10926 Cov.: 32 AF XY: 0.357 AC XY: 26536 AN XY: 74366

Gnomad4 AFR AF: 0.517

Gnomad4 AMR AF: 0.390

Gnomad4 ASJ AF: 0.285

Gnomad4 EAS AF: 0.689

Gnomad4 SAS AF: 0.365

Gnomad4 FIN AF: 0.240

Gnomad4 NFE AF: 0.244

Gnomad4 OTH AF: 0.379

Alfa AF: 0.268 Hom.: 8016

Bravo AF: 0.375

Asia WGS AF: 0.540 AC: 1876 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Oct 16, 2018

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
Cadd	Benign	0.71
Dann	Benign	0.38

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		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: rs3733001; hg19: chr3-186938956; COSMIC: COSV61830109;