dbSNP rs11003123: MBL2:c.-9-130C>T (chr10-52771774-G-A) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_001378373.1(MBL2):c.-9-130C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.229 in 1,332,208 control chromosomes in the GnomAD database, including 38,605 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 ( 7902 hom., cov: 32)

Exomes 𝑓: 0.22 ( 30703 hom. )

Consequence

MBL2
NM_001378373.1 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.0150

Publications

20 publications found

Variant links:

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]

MBL2 links:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.81).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.502 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein	UniProt
MBL2	NM_001378373.1 link	c.-9-130C>T	intron_variant	Intron 1 of 4	ENST00000674931.1	NP_001365302.1
MBL2	NM_001378374.1 link	c.-24-115C>T	intron_variant	Intron 1 of 4		NP_001365303.1
MBL2	NM_000242.3 link	c.-139C>T	upstream_gene_variant			NP_000233.1	P11226

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein	UniProt
MBL2	ENST00000674931.1 link	c.-9-130C>T	intron_variant	Intron 1 of 4		NM_001378373.1	ENSP00000502789.1	P11226
MBL2	ENST00000675947.1 link	c.-24-115C>T	intron_variant	Intron 1 of 4			ENSP00000502615.1	P11226
MBL2	ENST00000373968.3 link	c.-139C>T	upstream_gene_variant		1		ENSP00000363079.3	P11226

Frequencies

GnomAD3 genomes

AF:

0.293

AC:

44495

AN:

151964

Hom.:

7889

Cov.:

show subpopulations

Gnomad AFR

AF:

0.508

Gnomad AMI

AF:

0.188

Gnomad AMR

AF:

0.213

Gnomad ASJ

AF:

0.263

Gnomad EAS

AF:

0.136

Gnomad SAS

AF:

0.246

Gnomad FIN

AF:

0.175

Gnomad MID

AF:

0.275

Gnomad NFE

AF:

0.217

Gnomad OTH

AF:

0.269

GnomAD4 exome

AF:

0.221

AC:

261155

AN:

1180126

Hom.:

30703

AF XY:

0.222

AC XY:

127578

AN XY:

575680

show subpopulations

African (AFR)

AF:

0.515

AC:

13129

AN:

25498

American (AMR)

AF:

0.179

AC:

3655

AN:

20368

Ashkenazi Jewish (ASJ)

AF:

0.259

AC:

4599

AN:

17754

East Asian (EAS)

AF:

0.139

AC:

4771

AN:

34270

South Asian (SAS)

AF:

0.236

AC:

13783

AN:

58412

European-Finnish (FIN)

AF:

0.174

AC:

6618

AN:

37994

Middle Eastern (MID)

AF:

0.229

AC:

794

AN:

3470

European-Non Finnish (NFE)

AF:

0.217

AC:

202605

AN:

932692

Other (OTH)

AF:

0.226

AC:

11201

AN:

49668

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.482

Heterozygous variant carriers

8870

17740

26611

35481

44351

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

7266

14532

21798

29064

36330

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.293

AC:

44541

AN:

152082

Hom.:

7902

Cov.:

AF XY:

0.288

AC XY:

21420

AN XY:

74336

show subpopulations

African (AFR)

AF:

0.508

AC:

21074

AN:

41484

American (AMR)

AF:

0.212

AC:

3244

AN:

15268

Ashkenazi Jewish (ASJ)

AF:

0.263

AC:

911

AN:

3460

East Asian (EAS)

AF:

0.137

AC:

707

AN:

5166

South Asian (SAS)

AF:

0.246

AC:

1183

AN:

4818

European-Finnish (FIN)

AF:

0.175

AC:

1849

AN:

10578

Middle Eastern (MID)

AF:

0.279

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.217

AC:

14758

AN:

67988

Other (OTH)

AF:

0.266

AC:

562

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

1512

3024

4537

6049

7561

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

434

868

1302

1736

2170

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.245

Hom.:

18346

Bravo

AF:

0.303

Asia WGS

AF:

0.186

AC:

648

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.81

CADD

Benign

3.1

(source)

DANN

Benign

0.75

PhyloP100

0.015

PromoterAI

0.027

Neutral

(source)

Mutation Taster

=100/0

polymorphism

(source)

Splicing

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

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over