rs710469

Positions:

• chr3-187266730-G-A
• chr3-187266730-G-C

Variant summary

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

The ENST00000296280.11(MASP1):​c.238-4010C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.477 in 151,976 control chromosomes in the GnomAD database, including 17,632 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 0.48 (17632 hom., cov: 31)
• Consequence: MASP1 ENST00000296280.11 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.257

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 (AMR) allele frequency at 95% confidence interval = 0.559 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MASP1	NM_001879.6	c.238-4010C>T		intron_variant		ENST00000337774.10	NP_001870.3
MASP1	NM_139125.4	c.238-4010C>T		intron_variant		ENST00000296280.11	NP_624302.1
MASP1	NM_001031849.3	c.238-4010C>T		intron_variant			NP_001027019.1
MASP1	NR_033519.2	n.111-4010C>T		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MASP1	ENST00000296280.11	c.238-4010C>T		intron_variant		1	NM_139125.4	ENSP00000296280
MASP1	ENST00000337774.10	c.238-4010C>T		intron_variant		1	NM_001879.6	ENSP00000336792	P1

Frequencies

GnomAD3 genomes AF: 0.477 AC: 72468 AN: 151856 Hom.: 17618 Cov.: 31

Gnomad AFR AF: 0.367

Gnomad AMI AF: 0.563

Gnomad AMR AF: 0.569

Gnomad ASJ AF: 0.491

Gnomad EAS AF: 0.532

Gnomad SAS AF: 0.568

Gnomad FIN AF: 0.560

Gnomad MID AF: 0.478

Gnomad NFE AF: 0.498

Gnomad OTH AF: 0.475

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

GnomAD4 genome AF: 0.477 AC: 72507 AN: 151976 Hom.: 17632 Cov.: 31 AF XY: 0.481 AC XY: 35759 AN XY: 74290

Gnomad4 AFR AF: 0.367

Gnomad4 AMR AF: 0.569

Gnomad4 ASJ AF: 0.491

Gnomad4 EAS AF: 0.532

Gnomad4 SAS AF: 0.567

Gnomad4 FIN AF: 0.560

Gnomad4 NFE AF: 0.498

Gnomad4 OTH AF: 0.478

Alfa AF: 0.483 Hom.: 16263

Bravo AF: 0.472

Asia WGS AF: 0.542 AC: 1889 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	0.70
DANN	Benign	0.41

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: rs710469; hg19: chr3-186984518;