Genetic Variant NM_001378373.1:c.188-90T>C (chr10-52770876-A-G) – 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.188-90T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.545 in 655,040 control chromosomes in the GnomAD database, including 100,694 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 ( 20063 hom., cov: 33)

Exomes 𝑓: 0.56 ( 80631 hom. )

Consequence

MBL2
NM_001378373.1 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.135

Publications

13 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:

Genome browser will be placed here

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=-0.82).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.63 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein	UniProt
MBL2	NM_001378373.1 link	c.188-90T>C	intron_variant	Intron 2 of 4	ENST00000674931.1	NP_001365302.1
MBL2	NM_000242.3 link	c.188-90T>C	intron_variant	Intron 1 of 3		NP_000233.1	P11226
MBL2	NM_001378374.1 link	c.188-90T>C	intron_variant	Intron 2 of 4		NP_001365303.1

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein	UniProt
MBL2	ENST00000674931.1 link	c.188-90T>C	intron_variant	Intron 2 of 4		NM_001378373.1	ENSP00000502789.1	P11226
MBL2	ENST00000373968.3 link	c.188-90T>C	intron_variant	Intron 1 of 3	1		ENSP00000363079.3	P11226
MBL2	ENST00000675947.1 link	c.188-90T>C	intron_variant	Intron 2 of 4			ENSP00000502615.1	P11226

Frequencies

GnomAD3 genomes

AF:

0.495

AC:

75153

AN:

151964

Hom.:

20037

Cov.:

show subpopulations

Gnomad AFR

AF:

0.276

Gnomad AMI

AF:

0.747

Gnomad AMR

AF:

0.626

Gnomad ASJ

AF:

0.579

Gnomad EAS

AF:

0.647

Gnomad SAS

AF:

0.495

Gnomad FIN

AF:

0.619

Gnomad MID

AF:

0.487

Gnomad NFE

AF:

0.559

Gnomad OTH

AF:

0.512

GnomAD4 exome

AF:

0.561

AC:

282109

AN:

502958

Hom.:

80631

AF XY:

0.559

AC XY:

144059

AN XY:

257632

show subpopulations

African (AFR)

AF:

0.267

AC:

3366

AN:

12616

American (AMR)

AF:

0.716

AC:

12638

AN:

17642

Ashkenazi Jewish (ASJ)

AF:

0.587

AC:

6735

AN:

11466

East Asian (EAS)

AF:

0.671

AC:

18910

AN:

28162

South Asian (SAS)

AF:

0.499

AC:

9161

AN:

18372

European-Finnish (FIN)

AF:

0.622

AC:

20826

AN:

33464

Middle Eastern (MID)

AF:

0.534

AC:

1464

AN:

2742

European-Non Finnish (NFE)

AF:

0.552

AC:

195110

AN:

353394

Other (OTH)

AF:

0.554

AC:

13899

AN:

25100

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

6272

12545

18817

25090

31362

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

3846

7692

11538

15384

19230

<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:

0.495

AC:

75215

AN:

152082

Hom.:

20063

Cov.:

AF XY:

0.502

AC XY:

37286

AN XY:

74326

show subpopulations

African (AFR)

AF:

0.276

AC:

11446

AN:

41512

American (AMR)

AF:

0.627

AC:

9579

AN:

15286

Ashkenazi Jewish (ASJ)

AF:

0.579

AC:

2004

AN:

3462

East Asian (EAS)

AF:

0.648

AC:

3347

AN:

5162

South Asian (SAS)

AF:

0.494

AC:

2379

AN:

4820

European-Finnish (FIN)

AF:

0.619

AC:

6535

AN:

10560

Middle Eastern (MID)

AF:

0.503

AC:

148

AN:

294

European-Non Finnish (NFE)

AF:

0.559

AC:

38006

AN:

67966

Other (OTH)

AF:

0.517

AC:

1090

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.493

Heterozygous variant carriers

1809

3618

5428

7237

9046

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

666

1332

1998

2664

3330

<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:

0.535

Hom.:

59984

Bravo

AF:

0.491

Asia WGS

AF:

0.594

AC:

2065

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.82

CADD

Benign

9.9

(source)

DANN

Benign

0.84

PhyloP100

-0.14

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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