Genetic Variant MRC1:p.Ile404Ile (chr10-17849727-C-T) – ACMG Classification: Benign (-13 pts)

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_StrongBP7BA1

The NM_002438.4(MRC1):c.1212C>T(p.Ile404Ile) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.798 in 780,510 control chromosomes in the GnomAD database, including 250,328 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 0.76 ( 44052 hom., cov: 31)

Exomes 𝑓: 0.81 ( 206276 hom. )

Consequence

MRC1
NM_002438.4 synonymous

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -3.38

Publications

7 publications found

Variant links:

Genes affected

MRC1 (HGNC:7228): (mannose receptor C-type 1) The recognition of complex carbohydrate structures on glycoproteins is an important part of several biological processes, including cell-cell recognition, serum glycoprotein turnover, and neutralization of pathogens. The protein encoded by this gene is a type I membrane receptor that mediates the endocytosis of glycoproteins by macrophages. The protein has been shown to bind high-mannose structures on the surface of potentially pathogenic viruses, bacteria, and fungi so that they can be neutralized by phagocytic engulfment.[provided by RefSeq, Sep 2015]

MRC1 links:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -13 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.74).

BP7

Synonymous conserved (PhyloP=-3.38 with no splicing effect.

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.845 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MRC1	NM_002438.4 link	c.1212C>T	p.Ile404Ile	synonymous_variant	Exon 7 of 30	ENST00000569591.3	NP_002429.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MRC1	ENST00000569591.3 link	c.1212C>T	p.Ile404Ile	synonymous_variant	Exon 7 of 30	1	NM_002438.4	ENSP00000455897.1

Frequencies

GnomAD3 genomes

AF:

0.757

AC:

114894

AN:

151696

Hom.:

44032

Cov.:

show subpopulations

Gnomad AFR

AF:

0.635

Gnomad AMI

AF:

0.733

Gnomad AMR

AF:

0.806

Gnomad ASJ

AF:

0.834

Gnomad EAS

AF:

0.828

Gnomad SAS

AF:

0.866

Gnomad FIN

AF:

0.871

Gnomad MID

AF:

0.807

Gnomad NFE

AF:

0.786

Gnomad OTH

AF:

0.769

GnomAD2 exomes

AF:

0.0000825

AC:

AN:

72704

AF XY:

0.0000503

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000137

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00153

GnomAD4 exome

AF:

0.808

AC:

508046

AN:

628696

Hom.:

206276

Cov.:

AF XY:

0.810

AC XY:

277530

AN XY:

342490

show subpopulations

African (AFR)

AF:

0.635

AC:

11230

AN:

17686

American (AMR)

AF:

0.866

AC:

37874

AN:

43734

Ashkenazi Jewish (ASJ)

AF:

0.830

AC:

17406

AN:

20982

East Asian (EAS)

AF:

0.809

AC:

29186

AN:

36064

South Asian (SAS)

AF:

0.859

AC:

59954

AN:

69794

European-Finnish (FIN)

AF:

0.873

AC:

46405

AN:

53144

Middle Eastern (MID)

AF:

0.807

AC:

3344

AN:

4146

European-Non Finnish (NFE)

AF:

0.790

AC:

276401

AN:

350048

Other (OTH)

AF:

0.793

AC:

26246

AN:

33098

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

5912

11823

17735

23646

29558

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

1412

2824

4236

5648

7060

<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:

0.757

AC:

114964

AN:

151814

Hom.:

44052

Cov.:

AF XY:

0.763

AC XY:

56638

AN XY:

74188

show subpopulations

African (AFR)

AF:

0.635

AC:

26266

AN:

41396

American (AMR)

AF:

0.807

AC:

12309

AN:

15254

Ashkenazi Jewish (ASJ)

AF:

0.834

AC:

2893

AN:

3470

East Asian (EAS)

AF:

0.828

AC:

4270

AN:

5156

South Asian (SAS)

AF:

0.867

AC:

4164

AN:

4804

European-Finnish (FIN)

AF:

0.871

AC:

9172

AN:

10534

Middle Eastern (MID)

AF:

0.796

AC:

234

AN:

294

European-Non Finnish (NFE)

AF:

0.786

AC:

53374

AN:

67894

Other (OTH)

AF:

0.768

AC:

1618

AN:

2106

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.505

Heterozygous variant carriers

1380

2759

4139

5518

6898

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

852

1704

2556

3408

4260

<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:

0.570

Hom.:

643

Bravo

AF:

0.746

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.74

CADD

Benign

0.014

(source)

DANN

Benign

0.73

PhyloP100

-3.4

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.030

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