dbSNP rs1443502: MRC1:p.Thr727Thr (chr10-17870917-T-C) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_002438.4(MRC1):c.2181T>C(p.Thr727Thr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.237 in 872,024 control chromosomes in the GnomAD database, including 28,419 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 0.22 ( 4247 hom., cov: 32)

Exomes 𝑓: 0.24 ( 24172 hom. )

Consequence

MRC1
NM_002438.4 synonymous

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.63

Publications

2 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 -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.64).

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.294 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MRC1	NM_002438.4 link	c.2181T>C	p.Thr727Thr	synonymous_variant	Exon 14 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.2181T>C	p.Thr727Thr	synonymous_variant	Exon 14 of 30	1	NM_002438.4	ENSP00000455897.1		P22897-1

Frequencies

GnomAD3 genomes

AF:

0.219

AC:

33281

AN:

152060

Hom.:

4247

Cov.:

show subpopulations

Gnomad AFR

AF:

0.129

Gnomad AMI

AF:

0.395

Gnomad AMR

AF:

0.165

Gnomad ASJ

AF:

0.172

Gnomad EAS

AF:

0.00481

Gnomad SAS

AF:

0.115

Gnomad FIN

AF:

0.297

Gnomad MID

AF:

0.206

Gnomad NFE

AF:

0.298

Gnomad OTH

AF:

0.203

GnomAD4 exome

AF:

0.241

AC:

173600

AN:

719846

Hom.:

24172

Cov.:

AF XY:

0.238

AC XY:

91424

AN XY:

384308

show subpopulations

African (AFR)

AF:

0.128

AC:

2537

AN:

19848

American (AMR)

AF:

0.119

AC:

5230

AN:

43876

Ashkenazi Jewish (ASJ)

AF:

0.185

AC:

3978

AN:

21480

East Asian (EAS)

AF:

0.00214

AC:

AN:

36492

South Asian (SAS)

AF:

0.121

AC:

8644

AN:

71702

European-Finnish (FIN)

AF:

0.300

AC:

15966

AN:

53166

Middle Eastern (MID)

AF:

0.202

AC:

871

AN:

4308

European-Non Finnish (NFE)

AF:

0.296

AC:

128104

AN:

432976

Other (OTH)

AF:

0.228

AC:

8192

AN:

35998

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.472

Heterozygous variant carriers

7911

15821

23732

31642

39553

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

1544

3088

4632

6176

7720

<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:

0.219

AC:

33291

AN:

152178

Hom.:

4247

Cov.:

AF XY:

0.216

AC XY:

16063

AN XY:

74406

show subpopulations

African (AFR)

AF:

0.129

AC:

5378

AN:

41536

American (AMR)

AF:

0.165

AC:

2524

AN:

15290

Ashkenazi Jewish (ASJ)

AF:

0.172

AC:

597

AN:

3470

East Asian (EAS)

AF:

0.00482

AC:

AN:

5188

South Asian (SAS)

AF:

0.115

AC:

554

AN:

4828

European-Finnish (FIN)

AF:

0.297

AC:

3146

AN:

10576

Middle Eastern (MID)

AF:

0.218

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.297

AC:

20221

AN:

67970

Other (OTH)

AF:

0.200

AC:

422

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

1263

2525

3788

5050

6313

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

352

704

1056

1408

1760

<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:

0.245

Hom.:

476

Bravo

AF:

0.205

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.64

CADD

Benign

6.0

(source)

DANN

Benign

0.73

PhyloP100

-1.6

Mutation Taster

=100/0

polymorphism

(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