3-187221403-T-A

Position:

• chr3-187221403-T-A

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_001879.6(MASP1):​c.1810-269A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.358 in 152,088 control chromosomes in the GnomAD database, including 11,100 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.36 (11100 hom., cov: 32)
• Consequence: MASP1 NM_001879.6 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.479

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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BP6: Variant 3-187221403-T-A is Benign according to our data. Variant chr3-187221403-T-A is described in ClinVar as [Benign]. Clinvar id is 1259259.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.67 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MASP1	NM_001879.6	c.1810-269A>T		intron_variant		ENST00000337774.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MASP1	ENST00000337774.10	c.1810-269A>T		intron_variant		1	NM_001879.6	P1

Frequencies

GnomAD3 genomes AF: 0.357 AC: 54325 AN: 151970 Hom.: 11068 Cov.: 32

Gnomad AFR AF: 0.520

Gnomad AMI AF: 0.263

Gnomad AMR AF: 0.391

Gnomad ASJ AF: 0.287

Gnomad EAS AF: 0.689

Gnomad SAS AF: 0.404

Gnomad FIN AF: 0.240

Gnomad MID AF: 0.339

Gnomad NFE AF: 0.245

Gnomad OTH AF: 0.377

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

GnomAD4 genome AF: 0.358 AC: 54418 AN: 152088 Hom.: 11100 Cov.: 32 AF XY: 0.360 AC XY: 26786 AN XY: 74336

Gnomad4 AFR AF: 0.521

Gnomad4 AMR AF: 0.391

Gnomad4 ASJ AF: 0.287

Gnomad4 EAS AF: 0.689

Gnomad4 SAS AF: 0.404

Gnomad4 FIN AF: 0.240

Gnomad4 NFE AF: 0.245

Gnomad4 OTH AF: 0.380

Alfa AF: 0.301 Hom.: 914

Bravo AF: 0.377

Asia WGS AF: 0.564 AC: 1959 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Oct 16, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	4.0
DANN	Benign	0.37

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: rs3733003; hg19: chr3-186939191;