chr10-52772040-T-C

Variant names:

• chr10-52772040-T-C
• rs36014597
• NM_001378373.1:c.-9-396A>G

Variant summary

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

The NM_001378373.1(MBL2):​c.-9-396A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.293 in 152,000 control chromosomes in the GnomAD database, including 7,880 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 0.29 (7880 hom., cov: 32)
• Consequence: MBL2 NM_001378373.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.195
• Publications: 11 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=-0.88).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.503 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.-9-396A>G		intron	N/A	NP_001365302.1	P11226
	MBL2	NM_001378374.1		c.-24-381A>G		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.-9-396A>G		intron	N/A	ENSP00000502789.1	P11226
	MBL2	ENST00000675947.1		c.-24-381A>G		intron	N/A	ENSP00000502615.1	P11226
	MBL2	ENST00000877442.1		c.-9-396A>G		intron	N/A	ENSP00000547501.1

Frequencies

GnomAD3 genomes AF: 0.293 AC: 44429 AN: 151882 Hom.: 7867 Cov.: 32

Gnomad AFR AF: 0.509

Gnomad AMI AF: 0.184

Gnomad AMR AF: 0.212

Gnomad ASJ AF: 0.262

Gnomad EAS AF: 0.135

Gnomad SAS AF: 0.246

Gnomad FIN AF: 0.175

Gnomad MID AF: 0.261

Gnomad NFE AF: 0.217

Gnomad OTH AF: 0.270

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

GnomAD4 genome AF: 0.293 AC: 44475 AN: 152000 Hom.: 7880 Cov.: 32 AF XY: 0.288 AC XY: 21398 AN XY: 74316

African (AFR) AF: 0.509 AC: 21070 AN: 41386

American (AMR) AF: 0.211 AC: 3229 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.262 AC: 906 AN: 3456

East Asian (EAS) AF: 0.136 AC: 700 AN: 5160

South Asian (SAS) AF: 0.245 AC: 1183 AN: 4824

European-Finnish (FIN) AF: 0.175 AC: 1850 AN: 10590

Middle Eastern (MID) AF: 0.264 AC: 77 AN: 292

European-Non Finnish (NFE) AF: 0.217 AC: 14729 AN: 67990

Other (OTH) AF: 0.267 AC: 564 AN: 2112

Alfa AF: 0.255 Hom.: 693

Bravo AF: 0.304

Asia WGS AF: 0.187 AC: 650 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	3.0
DANN	Benign	0.47
PhyloP100		-0.20
PromoterAI		0.021	Neutral

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs36014597; hg19: chr10-54531800;