dbSNP rs2477664: MRC1:p.Ile260Ile (chr10-17833817-T-A) – 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.780T>A(p.Ile260Ile) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.494 in 780,750 control chromosomes in the GnomAD database, including 97,037 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 ( 18445 hom., cov: 33)

Exomes 𝑓: 0.50 ( 78592 hom. )

Consequence

MRC1
NM_002438.4 synonymous

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -2.84

Publications

13 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:

Genome browser will be placed here

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=-0.66).

BP7

Synonymous conserved (PhyloP=-2.84 with no splicing effect.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.535 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MRC1	NM_002438.4 link	c.780T>A	p.Ile260Ile	synonymous_variant	Exon 4 of 30	ENST00000569591.3	NP_002429.1	P22897-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MRC1	ENST00000569591.3 link	c.780T>A	p.Ile260Ile	synonymous_variant	Exon 4 of 30	1	NM_002438.4	ENSP00000455897.1		P22897-1

Frequencies

GnomAD3 genomes

AF:

0.490

AC:

74401

AN:

151860

Hom.:

18440

Cov.:

show subpopulations

Gnomad AFR

AF:

0.438

Gnomad AMI

AF:

0.591

Gnomad AMR

AF:

0.466

Gnomad ASJ

AF:

0.523

Gnomad EAS

AF:

0.441

Gnomad SAS

AF:

0.400

Gnomad FIN

AF:

0.453

Gnomad MID

AF:

0.462

Gnomad NFE

AF:

0.539

Gnomad OTH

AF:

0.495

GnomAD2 exomes

AF:

0.000450

AC:

AN:

186574

AF XY:

0.000525

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000146

Gnomad ASJ exome

AF:

0.000705

Gnomad EAS exome

AF:

0.000768

Gnomad FIN exome

AF:

0.000699

Gnomad NFE exome

AF:

0.000567

Gnomad OTH exome

AF:

0.000875

GnomAD4 exome

AF:

0.495

AC:

311455

AN:

628772

Hom.:

78592

Cov.:

AF XY:

0.492

AC XY:

168519

AN XY:

342530

show subpopulations

African (AFR)

AF:

0.440

AC:

7784

AN:

17694

American (AMR)

AF:

0.440

AC:

19252

AN:

43740

Ashkenazi Jewish (ASJ)

AF:

0.523

AC:

10984

AN:

20984

East Asian (EAS)

AF:

0.445

AC:

16037

AN:

36070

South Asian (SAS)

AF:

0.389

AC:

27171

AN:

69796

European-Finnish (FIN)

AF:

0.458

AC:

24338

AN:

53138

Middle Eastern (MID)

AF:

0.453

AC:

1877

AN:

4148

European-Non Finnish (NFE)

AF:

0.535

AC:

187476

AN:

350104

Other (OTH)

AF:

0.500

AC:

16536

AN:

33098

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

10242

20484

30727

40969

51211

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

1042

2084

3126

4168

5210

<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:

0.490

AC:

74438

AN:

151978

Hom.:

18445

Cov.:

AF XY:

0.485

AC XY:

36057

AN XY:

74278

show subpopulations

African (AFR)

AF:

0.438

AC:

18149

AN:

41430

American (AMR)

AF:

0.466

AC:

7120

AN:

15276

Ashkenazi Jewish (ASJ)

AF:

0.523

AC:

1814

AN:

3470

East Asian (EAS)

AF:

0.441

AC:

2273

AN:

5152

South Asian (SAS)

AF:

0.399

AC:

1926

AN:

4824

European-Finnish (FIN)

AF:

0.453

AC:

4777

AN:

10538

Middle Eastern (MID)

AF:

0.466

AC:

137

AN:

294

European-Non Finnish (NFE)

AF:

0.539

AC:

36659

AN:

67976

Other (OTH)

AF:

0.496

AC:

1044

AN:

2106

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

2029

4059

6088

8118

10147

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

672

1344

2016

2688

3360

<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:

0.495

Hom.:

1801

Bravo

AF:

0.487

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.66

CADD

Benign

0.41

(source)

DANN

Benign

0.76

PhyloP100

-2.8

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