10-52770307-A-G

Variant names:

• chr10-52770307-A-G
• rs4935047
• NM_001378373.1:c.304+363T>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.304+363T>C 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 152,126 control chromosomes in the GnomAD database, including 19,964 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 (19964 hom., cov: 33)
• Consequence: MBL2 NM_001378373.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.298
• Publications: 18 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=-0.81).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.63 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.304+363T>C		intron	N/A	NP_001365302.1
	MBL2	NM_000242.3		c.304+363T>C		intron	N/A	NP_000233.1
	MBL2	NM_001378374.1		c.304+363T>C		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.304+363T>C		intron	N/A	ENSP00000502789.1
	MBL2	ENST00000373968.3	TSL:1	c.304+363T>C		intron	N/A	ENSP00000363079.3
	MBL2	ENST00000675947.1		c.304+363T>C		intron	N/A	ENSP00000502615.1

Frequencies

GnomAD3 genomes AF: 0.492 AC: 74755 AN: 152008 Hom.: 19941 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: 0.647

Gnomad SAS AF: 0.495

Gnomad FIN AF: 0.618

Gnomad MID AF: 0.487

Gnomad NFE AF: 0.559

Gnomad OTH AF: 0.511

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

GnomAD4 genome AF: 0.492 AC: 74804 AN: 152126 Hom.: 19964 Cov.: 33 AF XY: 0.499 AC XY: 37081 AN XY: 74358

African (AFR) AF: 0.266 AC: 11030 AN: 41514

American (AMR) AF: 0.625 AC: 9565 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.579 AC: 2005 AN: 3460

East Asian (EAS) AF: 0.648 AC: 3346 AN: 5164

South Asian (SAS) AF: 0.494 AC: 2379 AN: 4816

European-Finnish (FIN) AF: 0.618 AC: 6535 AN: 10570

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

European-Non Finnish (NFE) AF: 0.559 AC: 38024 AN: 67988

Other (OTH) AF: 0.517 AC: 1091 AN: 2112

Alfa AF: 0.535 Hom.: 11487

Bravo AF: 0.488

Asia WGS AF: 0.592 AC: 2058 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	1.5
DANN	Benign	0.77
PhyloP100		-0.30
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: rs4935047; hg19: chr10-54530067;