NM_001378373.1:c.305-182T>C

Variant names:

• chr10-52769497-A-G
• rs1838065
• NM_001378373.1:c.305-182T>C

Variant summary

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

The NM_001378373.1(MBL2):​c.305-182T>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
• Publications: 23 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=-0.89).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.46 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MBL2	NM_001378373.1	MANE Select	c.305-182T>C		intron	N/A	NP_001365302.1	P11226
	MBL2	NM_000242.3		c.305-182T>C		intron	N/A	NP_000233.1	P11226
	MBL2	NM_001378374.1		c.305-182T>C		intron	N/A	NP_001365303.1	P11226

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MBL2	ENST00000674931.1	MANE Select	c.305-182T>C		intron	N/A	ENSP00000502789.1	P11226
	MBL2	ENST00000373968.3	TSL:1	c.305-182T>C		intron	N/A	ENSP00000363079.3	P11226
	MBL2	ENST00000675947.1		c.305-182T>C		intron	N/A	ENSP00000502615.1	P11226

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

African (AFR) AF: 0.127 AC: 5239 AN: 41254

American (AMR) AF: 0.407 AC: 6217 AN: 15260

Ashkenazi Jewish (ASJ) AF: 0.391 AC: 1353 AN: 3458

East Asian (EAS) AF: 0.476 AC: 2458 AN: 5168

South Asian (SAS) AF: 0.341 AC: 1646 AN: 4822

European-Finnish (FIN) AF: 0.405 AC: 4282 AN: 10576

Middle Eastern (MID) AF: 0.323 AC: 93 AN: 288

European-Non Finnish (NFE) AF: 0.373 AC: 25381 AN: 67980

Other (OTH) AF: 0.318 AC: 670 AN: 2108

Alfa AF: 0.360 Hom.: 29532

Bravo AF: 0.312

Asia WGS AF: 0.430 AC: 1492 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	4.3
DANN	Benign	0.24
PhyloP100		0.23
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: rs1838065; hg19: chr10-54529257;