rs698090

Variant names:

• chr3-187246512-C-T
• rs698090
• ENST00000169293.10:c.*821G>A

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 18 publications found

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]

MASP1 Gene-Disease associations (from GenCC):

• 3MC syndrome 1

  Inheritance: AR Classification: DEFINITIVE, STRONG Submitted by: G2P, PanelApp Australia, Labcorp Genetics (formerly Invitae)
• 3MC syndrome

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000169293.10. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MASP1	NM_139125.4	MANE Select	c.1091-2891G>A		intron	N/A	NP_624302.1
	MASP1	NM_001879.6	MANE Plus Clinical	c.1091-2891G>A		intron	N/A	NP_001870.3
	MASP1	NM_001031849.3		c.*821G>A		3_prime_UTR	Exon 9 of 9	NP_001027019.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MASP1	ENST00000169293.10	TSL:1	c.*821G>A		3_prime_UTR	Exon 9 of 9	ENSP00000169293.6
	MASP1	ENST00000296280.11	TSL:1 MANE Select	c.1091-2891G>A		intron	N/A	ENSP00000296280.7
	MASP1	ENST00000337774.10	TSL:1 MANE Plus Clinical	c.1091-2891G>A		intron	N/A	ENSP00000336792.5

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

African (AFR) AF: 0.376 AC: 5942 AN: 15786

American (AMR) AF: 0.759 AC: 747 AN: 984

Ashkenazi Jewish (ASJ) AF: 0.555 AC: 2861 AN: 5152

East Asian (EAS) AF: 0.659 AC: 2391 AN: 3630

South Asian (SAS) AF: 0.499 AC: 8207 AN: 16458

European-Finnish (FIN) AF: 0.683 AC: 190 AN: 278

Middle Eastern (MID) AF: 0.597 AC: 967 AN: 1620

European-Non Finnish (NFE) AF: 0.643 AC: 490219 AN: 761878

Other (OTH) AF: 0.610 AC: 16651 AN: 27296

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

African (AFR) AF: 0.406 AC: 16795 AN: 41402

American (AMR) AF: 0.715 AC: 10937 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.570 AC: 1978 AN: 3470

East Asian (EAS) AF: 0.635 AC: 3278 AN: 5162

South Asian (SAS) AF: 0.491 AC: 2363 AN: 4816

European-Finnish (FIN) AF: 0.681 AC: 7203 AN: 10578

Middle Eastern (MID) AF: 0.565 AC: 166 AN: 294

European-Non Finnish (NFE) AF: 0.645 AC: 43814 AN: 67950

Other (OTH) AF: 0.623 AC: 1310 AN: 2102

Alfa AF: 0.614 Hom.: 17842

Bravo AF: 0.583

Asia WGS AF: 0.558 AC: 1946 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.59
DANN	Benign	0.57
PhyloP100		-0.032
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: rs698090; hg19: chr3-186964300;