Genetic Variant MBL2:c.-9-171A>T (chr10-52771815-T-A) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBS1BS2

The NM_001378373.1(MBL2):c.-9-171A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00152 in 898,218 control chromosomes in the GnomAD database, including 16 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 0.0061 ( 10 hom., cov: 33)

Exomes 𝑓: 0.00059 ( 6 hom. )

Consequence

MBL2
NM_001378373.1 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.774

Publications

3 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=-0.8).

BS1

Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.00609 (928/152326) while in subpopulation AFR AF = 0.0211 (878/41574). AF 95% confidence interval is 0.02. There are 10 homozygotes in GnomAd4. There are 418 alleles in the male GnomAd4 subpopulation. Median coverage is 33. This position passed quality control check.

BS2

High AC in GnomAd4 at 928 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

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
MBL2	NM_001378373.1	MANE Select	c.-9-171A>T	intron	N/A	NP_001365302.1	P11226
MBL2	NM_001378374.1		c.-24-156A>T	intron	N/A	NP_001365303.1	P11226
MBL2	NM_000242.3		c.-180A>T	upstream_gene	N/A	NP_000233.1	P11226

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
MBL2	ENST00000674931.1	MANE Select	c.-9-171A>T	intron	N/A	ENSP00000502789.1	P11226
MBL2	ENST00000675947.1		c.-24-156A>T	intron	N/A	ENSP00000502615.1	P11226
MBL2	ENST00000877442.1		c.-9-171A>T	intron	N/A	ENSP00000547501.1

Frequencies

GnomAD3 genomes

AF:

0.00608

AC:

926

AN:

152208

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0211

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00242

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000132

Gnomad OTH

AF:

0.00191

GnomAD4 exome

AF:

0.000586

AC:

437

AN:

745892

Hom.:

AF XY:

0.000506

AC XY:

190

AN XY:

375254

show subpopulations

African (AFR)

AF:

0.0197

AC:

343

AN:

17420

American (AMR)

AF:

0.00142

AC:

AN:

19006

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

14680

East Asian (EAS)

AF:

0.00

AC:

AN:

31994

South Asian (SAS)

AF:

0.000191

AC:

AN:

47156

European-Finnish (FIN)

AF:

0.00

AC:

AN:

29484

Middle Eastern (MID)

AF:

0.00

AC:

AN:

2520

European-Non Finnish (NFE)

AF:

0.0000419

AC:

AN:

548622

Other (OTH)

AF:

0.00100

AC:

AN:

35010

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

111

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

<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:

0.00609

AC:

928

AN:

152326

Hom.:

Cov.:

AF XY:

0.00561

AC XY:

418

AN XY:

74502

show subpopulations

African (AFR)

AF:

0.0211

AC:

878

AN:

41574

American (AMR)

AF:

0.00242

AC:

AN:

15304

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3468

East Asian (EAS)

AF:

0.00

AC:

AN:

5184

South Asian (SAS)

AF:

0.00

AC:

AN:

4826

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10626

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.000132

AC:

AN:

68024

Other (OTH)

AF:

0.00189

AC:

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

127

169

211

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

100

<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:

0.00140

Hom.:

Bravo

AF:

0.00692

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.80

CADD

Benign

0.49

(source)

DANN

Benign

0.62

PhyloP100

-0.77

PromoterAI

-0.0022

Neutral

(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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over