3-187220496-C-CTTT

Position:

• chr3-187220496-C-CTTT

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_Moderate BS1 BS2

The NM_001879.6(MASP1):​c.1910-236_1910-235insAAA variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00402 in 127,732 control chromosomes in the GnomAD database, including 15 homozygotes. Variant has been reported in ClinVar as Likely benign (★).

• Frequency: Genomes: 𝑓 0.0040 (15 hom., cov: 22)
• Consequence: MASP1 NM_001879.6 intron
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.667

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 -10 ACMG points.

• BP6: Variant 3-187220496-C-CTTT is Benign according to our data. Variant chr3-187220496-C-CTTT is described in ClinVar as [Likely_benign]. Clinvar id is 1199019.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00402 (513/127732) while in subpopulation AFR AF= 0.0142 (463/32716). AF 95% confidence interval is 0.0131. There are 15 homozygotes in gnomad4. There are 249 alleles in male gnomad4 subpopulation. Median coverage is 22. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd4 at 15 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MASP1	NM_001879.6	c.1910-236_1910-235insAAA		intron_variant		ENST00000337774.10	NP_001870.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MASP1	ENST00000337774.10	c.1910-236_1910-235insAAA		intron_variant		1	NM_001879.6	ENSP00000336792	P1

Frequencies

GnomAD3 genomes AF: 0.00403 AC: 515 AN: 127746 Hom.: 15 Cov.: 22

Gnomad AFR AF: 0.0142

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00150

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000510

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00769

Gnomad NFE AF: 0.000337

Gnomad OTH AF: 0.00462

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

GnomAD4 genome AF: 0.00402 AC: 513 AN: 127732 Hom.: 15 Cov.: 22 AF XY: 0.00410 AC XY: 249 AN XY: 60794

Gnomad4 AFR AF: 0.0142

Gnomad4 AMR AF: 0.00150

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000513

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000337

Gnomad4 OTH AF: 0.00460

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

GeneDx

Nov 02, 2019

- -

Computational scores

Source: dbNSFP v4.3

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs376566294; hg19: chr3-186938284;