rs34120190

Variant names:

• chr10-52771504-G-A
• rs34120190
• NM_001378373.1:c.132C>T

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_Strong BP6 BP7 BS2

The NM_001378373.1(MBL2):​c.132C>T​(p.Asn44Asn) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00129 in 1,613,864 control chromosomes in the GnomAD database, including 22 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).

• Frequency:
  • Genomes: 𝑓 0.0011 (3 hom., cov: 32)
  • Exomes 𝑓: 0.0013 (19 hom.)
• Consequence: MBL2 NM_001378373.1 synonymous
• Clinical Significance: Conflicting classifications of pathogenicity criteria provided, conflicting classifications U:1 B:3
• Conservation: PhyloP100: -2.09
• Publications: 3 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 -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BP6: Variant 10-52771504-G-A is Benign according to our data. Variant chr10-52771504-G-A is described in ClinVar as Conflicting_classifications_of_pathogenicity. ClinVar VariationId is 403073.
• BP7: Synonymous conserved (PhyloP=-2.09 with no splicing effect.
• BS2: High AC in GnomAd4 at 168 AD gene.

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.132C>T	p.Asn44Asn	synonymous	Exon 2 of 5	NP_001365302.1
	MBL2	NM_000242.3		c.132C>T	p.Asn44Asn	synonymous	Exon 1 of 4	NP_000233.1
	MBL2	NM_001378374.1		c.132C>T	p.Asn44Asn	synonymous	Exon 2 of 5	NP_001365303.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MBL2	ENST00000674931.1	MANE Select	c.132C>T	p.Asn44Asn	synonymous	Exon 2 of 5	ENSP00000502789.1
	MBL2	ENST00000373968.3	TSL:1	c.132C>T	p.Asn44Asn	synonymous	Exon 1 of 4	ENSP00000363079.3
	MBL2	ENST00000675947.1		c.132C>T	p.Asn44Asn	synonymous	Exon 2 of 5	ENSP00000502615.1

Frequencies

GnomAD3 genomes AF: 0.00110 AC: 167 AN: 152108 Hom.: 3 Cov.: 32

Gnomad AFR AF: 0.000217

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000851

Gnomad ASJ AF: 0.0147

Gnomad EAS AF: 0.000193

Gnomad SAS AF: 0.00642

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.0158

Gnomad NFE AF: 0.000750

Gnomad OTH AF: 0.00287

GnomAD2 exomes AF: 0.00208 AC: 523 AN: 251182 AF XY: 0.00259

Gnomad AFR exome AF: 0.000123

Gnomad AMR exome AF: 0.00113

Gnomad ASJ exome AF: 0.0120

Gnomad EAS exome AF: 0.000163

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000820

Gnomad OTH exome AF: 0.00245

GnomAD4 exome AF: 0.00131 AC: 1911 AN: 1461638 Hom.: 19 Cov.: 32 AF XY: 0.00153 AC XY: 1113 AN XY: 727114

African (AFR) AF: 0.000209 AC: 7 AN: 33472

American (AMR) AF: 0.00150 AC: 67 AN: 44716

Ashkenazi Jewish (ASJ) AF: 0.0119 AC: 310 AN: 26112

East Asian (EAS) AF: 0.000630 AC: 25 AN: 39700

South Asian (SAS) AF: 0.00775 AC: 668 AN: 86246

European-Finnish (FIN) AF: 0.0000936 AC: 5 AN: 53420

Middle Eastern (MID) AF: 0.0139 AC: 80 AN: 5760

European-Non Finnish (NFE) AF: 0.000553 AC: 615 AN: 1111834

Other (OTH) AF: 0.00222 AC: 134 AN: 60378

GnomAD4 genome AF: 0.00110 AC: 168 AN: 152226 Hom.: 3 Cov.: 32 AF XY: 0.00117 AC XY: 87 AN XY: 74436

African (AFR) AF: 0.000217 AC: 9 AN: 41538

American (AMR) AF: 0.000850 AC: 13 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.0147 AC: 51 AN: 3468

East Asian (EAS) AF: 0.000194 AC: 1 AN: 5164

South Asian (SAS) AF: 0.00642 AC: 31 AN: 4826

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10604

Middle Eastern (MID) AF: 0.0170 AC: 5 AN: 294

European-Non Finnish (NFE) AF: 0.000750 AC: 51 AN: 68006

Other (OTH) AF: 0.00331 AC: 7 AN: 2114

Alfa AF: 0.00168 Hom.: 0

Bravo AF: 0.000979

Asia WGS AF: 0.00318 AC: 11 AN: 3478

EpiCase AF: 0.00202

EpiControl AF: 0.00119

ClinVar

ClinVar submissions as Germline

Significance: Conflicting classifications of pathogenicity

Revision: criteria provided, conflicting classifications

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)
-	1	-	Mannose-binding lectin deficiency (1)
-	-	1	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	0.40
DANN	Benign	0.63
PhyloP100		-2.1
PromoterAI		-0.029	Neutral
Mutation Taster		=100/0	polymorphism

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: rs34120190; hg19: chr10-54531264; COSMIC: COSV64759430;