10-52769945-C-T

Variant names:

• chr10-52769945-C-T
• rs4935046
• NM_001378373.1:c.305-630G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001378373.1(MBL2):​c.305-630G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.492 in 152,098 control chromosomes in the GnomAD database, including 19,936 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 0.49 (19936 hom., cov: 33)
• Consequence: MBL2 NM_001378373.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.40
• Publications: 4 publications found

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

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.62 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001378373.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MBL2	NM_001378373.1	MANE Select	c.305-630G>A		intron	N/A	NP_001365302.1
	MBL2	NM_000242.3		c.305-630G>A		intron	N/A	NP_000233.1
	MBL2	NM_001378374.1		c.305-630G>A		intron	N/A	NP_001365303.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MBL2	ENST00000674931.1	MANE Select	c.305-630G>A		intron	N/A	ENSP00000502789.1
	MBL2	ENST00000373968.3	TSL:1	c.305-630G>A		intron	N/A	ENSP00000363079.3
	MBL2	ENST00000675947.1		c.305-630G>A		intron	N/A	ENSP00000502615.1

Frequencies

GnomAD3 genomes AF: 0.492 AC: 74713 AN: 151980 Hom.: 19913 Cov.: 33

Gnomad AFR AF: 0.266

Gnomad AMI AF: 0.747

Gnomad AMR AF: 0.625

Gnomad ASJ AF: 0.579

Gnomad EAS AF: 0.637

Gnomad SAS AF: 0.494

Gnomad FIN AF: 0.618

Gnomad MID AF: 0.487

Gnomad NFE AF: 0.560

Gnomad OTH AF: 0.512

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

GnomAD4 genome AF: 0.492 AC: 74762 AN: 152098 Hom.: 19936 Cov.: 33 AF XY: 0.498 AC XY: 37054 AN XY: 74346

African (AFR) AF: 0.266 AC: 11022 AN: 41508

American (AMR) AF: 0.625 AC: 9559 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.579 AC: 2009 AN: 3470

East Asian (EAS) AF: 0.638 AC: 3293 AN: 5160

South Asian (SAS) AF: 0.493 AC: 2378 AN: 4822

European-Finnish (FIN) AF: 0.618 AC: 6523 AN: 10556

Middle Eastern (MID) AF: 0.503 AC: 148 AN: 294

European-Non Finnish (NFE) AF: 0.560 AC: 38057 AN: 67982

Other (OTH) AF: 0.518 AC: 1092 AN: 2108

Alfa AF: 0.509 Hom.: 2699

Bravo AF: 0.488

Asia WGS AF: 0.589 AC: 2051 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	0.20
DANN	Benign	0.75
PhyloP100		-1.4
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs4935046; hg19: chr10-54529705;