rs1357134

Variant names:

• chr3-187261980-A-G
• rs1357134
• NM_139125.4:c.415+563T>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_139125.4(MASP1):​c.415+563T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.396 in 152,088 control chromosomes in the GnomAD database, including 12,102 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 0.40 (12102 hom., cov: 33)
• Consequence: MASP1 NM_139125.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.356
• Publications: 6 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=-0.85).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.42 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MASP1	NM_139125.4	c.415+563T>C		intron_variant	Intron 3 of 10	ENST00000296280.11	NP_624302.1
MASP1	NM_001879.6	c.415+563T>C		intron_variant	Intron 3 of 15	ENST00000337774.10	NP_001870.3
MASP1	NM_001031849.3	c.415+563T>C		intron_variant	Intron 3 of 8		NP_001027019.1
MASP1	NR_033519.2	n.288+563T>C		intron_variant	Intron 2 of 9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MASP1	ENST00000296280.11	c.415+563T>C		intron_variant	Intron 3 of 10	1	NM_139125.4	ENSP00000296280.7
MASP1	ENST00000337774.10	c.415+563T>C		intron_variant	Intron 3 of 15	1	NM_001879.6	ENSP00000336792.5

Frequencies

GnomAD3 genomes AF: 0.396 AC: 60231 AN: 151970 Hom.: 12092 Cov.: 33

Gnomad AFR AF: 0.424

Gnomad AMI AF: 0.380

Gnomad AMR AF: 0.303

Gnomad ASJ AF: 0.437

Gnomad EAS AF: 0.335

Gnomad SAS AF: 0.302

Gnomad FIN AF: 0.371

Gnomad MID AF: 0.427

Gnomad NFE AF: 0.414

Gnomad OTH AF: 0.396

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.396 AC: 60268 AN: 152088 Hom.: 12102 Cov.: 33 AF XY: 0.392 AC XY: 29178 AN XY: 74344

African (AFR) AF: 0.425 AC: 17614 AN: 41468

American (AMR) AF: 0.302 AC: 4619 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.437 AC: 1516 AN: 3468

East Asian (EAS) AF: 0.335 AC: 1735 AN: 5178

South Asian (SAS) AF: 0.300 AC: 1445 AN: 4816

European-Finnish (FIN) AF: 0.371 AC: 3927 AN: 10578

Middle Eastern (MID) AF: 0.415 AC: 122 AN: 294

European-Non Finnish (NFE) AF: 0.414 AC: 28116 AN: 67964

Other (OTH) AF: 0.391 AC: 827 AN: 2114

Alfa AF: 0.397 Hom.: 6435

Bravo AF: 0.392

Asia WGS AF: 0.325 AC: 1125 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	2.7
DANN	Benign	0.61
PhyloP100		0.36
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: rs1357134; hg19: chr3-186979768;