3-187261980-A-G

Position:

• chr3-187261980-A-G

Variant summary

Our verdict is Benign. Variant got -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

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=-0.85).
• 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/exons	MANE	UniProt
MASP1	NM_001879.6	c.415+563T>C		intron_variant		ENST00000337774.10
MASP1	NM_139125.4	c.415+563T>C		intron_variant		ENST00000296280.11
MASP1	NM_001031849.3	c.415+563T>C		intron_variant
MASP1	NR_033519.2	n.288+563T>C		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MASP1	ENST00000296280.11	c.415+563T>C		intron_variant		1	NM_139125.4
MASP1	ENST00000337774.10	c.415+563T>C		intron_variant		1	NM_001879.6	P1

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

Gnomad4 AFR AF: 0.425

Gnomad4 AMR AF: 0.302

Gnomad4 ASJ AF: 0.437

Gnomad4 EAS AF: 0.335

Gnomad4 SAS AF: 0.300

Gnomad4 FIN AF: 0.371

Gnomad4 NFE AF: 0.414

Gnomad4 OTH AF: 0.391

Alfa AF: 0.394 Hom.: 3744

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

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: rs1357134; hg19: chr3-186979768;