Genetic Variant NM_001378373.1:c.-9-86C>A (chr10-52771730-G-T) – 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.-9-86C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0172 in 1,487,464 control chromosomes in the GnomAD database, including 293 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 0.017 ( 24 hom., cov: 33)

Exomes 𝑓: 0.017 ( 269 hom. )

Consequence

MBL2
NM_001378373.1 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.211

Publications

7 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=-0.86).

BS1

Variant frequency is greater than expected in population sas. GnomAd4 allele frequency = 0.0172 (2625/152294) while in subpopulation SAS AF = 0.0328 (158/4824). AF 95% confidence interval is 0.0286. There are 24 homozygotes in GnomAd4. There are 1255 alleles in the male GnomAd4 subpopulation. Median coverage is 33. This position passed quality control check.

BS2

High AC in GnomAd4 at 2625 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein	UniProt
MBL2	NM_001378373.1 link	c.-9-86C>A	intron_variant	Intron 1 of 4	ENST00000674931.1	NP_001365302.1
MBL2	NM_001378374.1 link	c.-24-71C>A	intron_variant	Intron 1 of 4		NP_001365303.1
MBL2	NM_000242.3 link	c.-95C>A	upstream_gene_variant			NP_000233.1	P11226

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein	UniProt
MBL2	ENST00000674931.1 link	c.-9-86C>A	intron_variant	Intron 1 of 4		NM_001378373.1	ENSP00000502789.1	P11226
MBL2	ENST00000675947.1 link	c.-24-71C>A	intron_variant	Intron 1 of 4			ENSP00000502615.1	P11226
MBL2	ENST00000373968.3 link	c.-95C>A	upstream_gene_variant		1		ENSP00000363079.3	P11226

Frequencies

GnomAD3 genomes

AF:

0.0173

AC:

2627

AN:

152176

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0227

Gnomad AMI

AF:

0.00768

Gnomad AMR

AF:

0.0139

Gnomad ASJ

AF:

0.0219

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.0331

Gnomad FIN

AF:

0.00687

Gnomad MID

AF:

0.0348

Gnomad NFE

AF:

0.0163

Gnomad OTH

AF:

0.0177

GnomAD4 exome

AF:

0.0172

AC:

23001

AN:

1335170

Hom.:

269

Cov.:

AF XY:

0.0176

AC XY:

11487

AN XY:

650918

show subpopulations

African (AFR)

AF:

0.0216

AC:

644

AN:

29880

American (AMR)

AF:

0.00844

AC:

250

AN:

29616

Ashkenazi Jewish (ASJ)

AF:

0.0169

AC:

349

AN:

20608

East Asian (EAS)

AF:

0.0000567

AC:

AN:

35264

South Asian (SAS)

AF:

0.0310

AC:

2115

AN:

68244

European-Finnish (FIN)

AF:

0.00931

AC:

426

AN:

45770

Middle Eastern (MID)

AF:

0.0170

AC:

AN:

4474

European-Non Finnish (NFE)

AF:

0.0175

AC:

18288

AN:

1046178

Other (OTH)

AF:

0.0154

AC:

851

AN:

55136

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.442

Heterozygous variant carriers

909

1817

2726

3634

4543

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

770

1540

2310

3080

3850

<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:

0.0172

AC:

2625

AN:

152294

Hom.:

Cov.:

AF XY:

0.0169

AC XY:

1255

AN XY:

74476

show subpopulations

African (AFR)

AF:

0.0226

AC:

939

AN:

41562

American (AMR)

AF:

0.0139

AC:

213

AN:

15304

Ashkenazi Jewish (ASJ)

AF:

0.0219

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5174

South Asian (SAS)

AF:

0.0328

AC:

158

AN:

4824

European-Finnish (FIN)

AF:

0.00687

AC:

AN:

10622

Middle Eastern (MID)

AF:

0.0408

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0163

AC:

1110

AN:

68016

Other (OTH)

AF:

0.0175

AC:

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

138

277

415

554

692

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

108

144

180

<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:

0.0180

Hom.:

Bravo

AF:

0.0178

Asia WGS

AF:

0.0170

AC:

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.86

CADD

Benign

2.3

(source)

DANN

Benign

0.61

PhyloP100

0.21

PromoterAI

0.028

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

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over