3-187220985-C-A

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BS1 BS2

The NM_001879.6(MASP1):c.1909+50G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000983 in 1,503,172 control chromosomes in the GnomAD database, including 13 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0051 (9 hom., cov: 31)
  • Exomes 𝑓: 0.00052 (4 hom.)
• Consequence: MASP1 NM_001879.6 intron
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.29

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=-0.88).
• BP6: Variant 3-187220985-C-A is Benign according to our data. Variant chr3-187220985-C-A is described in ClinVar as [Likely_benign]. Clinvar id is 1328784.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00511 (778/152336) while in subpopulation AFR AF= 0.018 (750/41564). AF 95% confidence interval is 0.017. There are 9 homozygotes in gnomad4. There are 372 alleles in male gnomad4 subpopulation. Median coverage is 31. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd at 9 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MASP1	NM_001879.6	c.1909+50G>T		intron_variant		ENST00000337774.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MASP1	ENST00000337774.10	c.1909+50G>T		intron_variant		1	NM_001879.6	P1

Frequencies

GnomAD3 genomes AF: 0.00509 AC: 775 AN: 152218 Hom.: 9 Cov.: 31

Gnomad AFR AF: 0.0180

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00124

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000882

Gnomad OTH AF: 0.00144

GnomAD3 exomes AF: 0.00129 AC: 320 AN: 248840 Hom.: 2 AF XY: 0.000914 AC XY: 123 AN XY: 134614

Gnomad AFR exome AF: 0.0173

Gnomad AMR exome AF: 0.000667

Gnomad ASJ exome AF: 0.000199

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.0000329

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000107

Gnomad OTH exome AF: 0.000656

GnomAD4 exome AF: 0.000518 AC: 700 AN: 1350836 Hom.: 4 Cov.: 20 AF XY: 0.000392 AC XY: 266 AN XY: 678276

Gnomad4 AFR exome AF: 0.0174

Gnomad4 AMR exome AF: 0.000696

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000477

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000455

Gnomad4 OTH exome AF: 0.00117

GnomAD4 genome AF: 0.00511 AC: 778 AN: 152336 Hom.: 9 Cov.: 31 AF XY: 0.00499 AC XY: 372 AN XY: 74488

Gnomad4 AFR AF: 0.0180

Gnomad4 AMR AF: 0.00124

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000882

Gnomad4 OTH AF: 0.00142

Alfa AF: 0.00291 Hom.: 0

Bravo AF: 0.00542

Asia WGS AF: 0.000866 AC: 3 AN: 3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

GeneDx

May 13, 2021

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
Cadd	Benign	0.61
Dann	Benign	0.49

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs75655422; hg19: chr3-186938773;