3-187246512-C-T

Position:

• chr3-187246512-C-T

Variant summary

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

The ENST00000169293.10(MASP1):​c.*821G>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 0.626 in 985,056 control chromosomes in the GnomAD database, including 195,017 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 0.58 (26739 hom., cov: 31)
  • Exomes 𝑓: 0.63 (168278 hom.)
• Consequence: MASP1 ENST00000169293.10 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0320

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.704 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MASP1	NM_001879.6	c.1091-2891G>A		intron_variant		ENST00000337774.10
MASP1	NM_139125.4	c.1091-2891G>A		intron_variant		ENST00000296280.11
MASP1	NM_001031849.3	c.*821G>A		3_prime_UTR_variant	9/9
MASP1	NR_033519.2	n.964-2891G>A		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MASP1	ENST00000296280.11	c.1091-2891G>A		intron_variant		1	NM_139125.4
MASP1	ENST00000337774.10	c.1091-2891G>A		intron_variant		1	NM_001879.6	P1

Frequencies

GnomAD3 genomes AF: 0.582 AC: 88397 AN: 151856 Hom.: 26704 Cov.: 31

Gnomad AFR AF: 0.406

Gnomad AMI AF: 0.679

Gnomad AMR AF: 0.715

Gnomad ASJ AF: 0.570

Gnomad EAS AF: 0.634

Gnomad SAS AF: 0.489

Gnomad FIN AF: 0.681

Gnomad MID AF: 0.532

Gnomad NFE AF: 0.645

Gnomad OTH AF: 0.618

GnomAD4 exome AF: 0.634 AC: 528175 AN: 833082 Hom.: 168278 Cov.: 35 AF XY: 0.633 AC XY: 243537 AN XY: 384716

Gnomad4 AFR exome AF: 0.376

Gnomad4 AMR exome AF: 0.759

Gnomad4 ASJ exome AF: 0.555

Gnomad4 EAS exome AF: 0.659

Gnomad4 SAS exome AF: 0.499

Gnomad4 FIN exome AF: 0.683

Gnomad4 NFE exome AF: 0.643

Gnomad4 OTH exome AF: 0.610

GnomAD4 genome AF: 0.582 AC: 88463 AN: 151974 Hom.: 26739 Cov.: 31 AF XY: 0.586 AC XY: 43499 AN XY: 74254

Gnomad4 AFR AF: 0.406

Gnomad4 AMR AF: 0.715

Gnomad4 ASJ AF: 0.570

Gnomad4 EAS AF: 0.635

Gnomad4 SAS AF: 0.491

Gnomad4 FIN AF: 0.681

Gnomad4 NFE AF: 0.645

Gnomad4 OTH AF: 0.623

Alfa AF: 0.614 Hom.: 16205

Bravo AF: 0.583

Asia WGS AF: 0.558 AC: 1946 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.59
DANN	Benign	0.57

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: rs698090; hg19: chr3-186964300;