rs1838066

Variant names:

• chr10-52769565-A-G
• rs1838066
• NM_001378373.1:c.305-250T>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.305-250T>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 152,110 control chromosomes in the GnomAD database, including 8,631 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 0.32 (8631 hom., cov: 32)
• Consequence: MBL2 NM_001378373.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0140
• Publications: 19 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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MBL2	NM_001378373.1	c.305-250T>C		intron_variant	Intron 3 of 4	ENST00000674931.1	NP_001365302.1
MBL2	NM_000242.3	c.305-250T>C		intron_variant	Intron 2 of 3		NP_000233.1
MBL2	NM_001378374.1	c.305-250T>C		intron_variant	Intron 3 of 4		NP_001365303.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MBL2	ENST00000674931.1	c.305-250T>C		intron_variant	Intron 3 of 4		NM_001378373.1	ENSP00000502789.1
MBL2	ENST00000373968.3	c.305-250T>C		intron_variant	Intron 2 of 3	1		ENSP00000363079.3
MBL2	ENST00000675947.1	c.305-250T>C		intron_variant	Intron 3 of 4			ENSP00000502615.1

Frequencies

GnomAD3 genomes AF: 0.315 AC: 47896 AN: 151992 Hom.: 8622 Cov.: 32

Gnomad AFR AF: 0.130

Gnomad AMI AF: 0.459

Gnomad AMR AF: 0.407

Gnomad ASJ AF: 0.392

Gnomad EAS AF: 0.474

Gnomad SAS AF: 0.343

Gnomad FIN AF: 0.405

Gnomad MID AF: 0.313

Gnomad NFE AF: 0.373

Gnomad OTH AF: 0.311

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

GnomAD4 genome AF: 0.315 AC: 47916 AN: 152110 Hom.: 8631 Cov.: 32 AF XY: 0.320 AC XY: 23767 AN XY: 74358

African (AFR) AF: 0.130 AC: 5390 AN: 41542

American (AMR) AF: 0.408 AC: 6232 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.392 AC: 1353 AN: 3454

East Asian (EAS) AF: 0.475 AC: 2456 AN: 5166

South Asian (SAS) AF: 0.341 AC: 1642 AN: 4818

European-Finnish (FIN) AF: 0.405 AC: 4284 AN: 10574

Middle Eastern (MID) AF: 0.327 AC: 96 AN: 294

European-Non Finnish (NFE) AF: 0.373 AC: 25374 AN: 67956

Other (OTH) AF: 0.318 AC: 671 AN: 2112

Alfa AF: 0.354 Hom.: 3959

Bravo AF: 0.312

Asia WGS AF: 0.431 AC: 1498 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.91
DANN	Benign	0.62
PhyloP100		-0.014
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: rs1838066; hg19: chr10-54529325;