rs1838065

Positions:

• chr10-52769497-A-G

Variant summary

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

The NM_001378373.1(MBL2):​c.305-182T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.315 in 151,826 control chromosomes in the GnomAD database, including 8,624 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 0.31 (8624 hom., cov: 32)
• Consequence: MBL2 NM_001378373.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.228

Genes affected

MBL2 (HGNC:6922): (mannose binding lectin 2) This gene encodes the soluble mannose-binding lectin or mannose-binding protein found in serum. The protein encoded belongs to the collectin family and is an important element in the innate immune system. The protein recognizes and binds to mannose and N-acetylglucosamine on many microorganisms, including bacteria, yeast, and viruses including influenza virus, HIV and SARS-CoV. This binding activates the classical complement pathway. Deficiencies of this gene have been associated with susceptibility to autoimmune and infectious diseases. [provided by RefSeq, Jun 2020]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.46 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MBL2	NM_001378373.1	c.305-182T>C		intron_variant		ENST00000674931.1	NP_001365302.1
MBL2	NM_000242.3	c.305-182T>C		intron_variant			NP_000233.1
MBL2	NM_001378374.1	c.305-182T>C		intron_variant			NP_001365303.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MBL2	ENST00000674931.1	c.305-182T>C		intron_variant			NM_001378373.1	ENSP00000502789	P1
MBL2	ENST00000373968.3	c.305-182T>C		intron_variant		1		ENSP00000363079	P1
MBL2	ENST00000675947.1	c.305-182T>C		intron_variant				ENSP00000502615	P1

Frequencies

GnomAD3 genomes AF: 0.315 AC: 47738 AN: 151708 Hom.: 8615 Cov.: 32

Gnomad AFR AF: 0.127

Gnomad AMI AF: 0.458

Gnomad AMR AF: 0.407

Gnomad ASJ AF: 0.391

Gnomad EAS AF: 0.474

Gnomad SAS AF: 0.343

Gnomad FIN AF: 0.405

Gnomad MID AF: 0.310

Gnomad NFE AF: 0.373

Gnomad OTH AF: 0.312

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

GnomAD4 genome AF: 0.315 AC: 47757 AN: 151826 Hom.: 8624 Cov.: 32 AF XY: 0.319 AC XY: 23678 AN XY: 74220

Gnomad4 AFR AF: 0.127

Gnomad4 AMR AF: 0.407

Gnomad4 ASJ AF: 0.391

Gnomad4 EAS AF: 0.476

Gnomad4 SAS AF: 0.341

Gnomad4 FIN AF: 0.405

Gnomad4 NFE AF: 0.373

Gnomad4 OTH AF: 0.318

Alfa AF: 0.367 Hom.: 11492

Bravo AF: 0.312

Asia WGS AF: 0.430 AC: 1492 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	4.3
DANN	Benign	0.24

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: rs1838065; hg19: chr10-54529257;