Genetic Variant NM_002438.4:c.*416T>A (chr10-17910881-T-A) – 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.*416T>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.705 in 181,894 control chromosomes in the GnomAD database, including 46,010 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 0.71 ( 39061 hom., cov: 32)

Exomes 𝑓: 0.68 ( 6949 hom. )

Consequence

MRC1
NM_002438.4 3_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.143

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 -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.89).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.832 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MRC1	NM_002438.4 link	c.*416T>A		3_prime_UTR_variant	Exon 30 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.*416T>A		3_prime_UTR_variant	Exon 30 of 30	1	NM_002438.4	ENSP00000455897.1		P22897-1

Frequencies

GnomAD3 genomes

AF:

0.710

AC:

107888

AN:

151898

Hom.:

39011

Cov.:

show subpopulations

Gnomad AFR

AF:

0.839

Gnomad AMI

AF:

0.610

Gnomad AMR

AF:

0.653

Gnomad ASJ

AF:

0.641

Gnomad EAS

AF:

0.482

Gnomad SAS

AF:

0.616

Gnomad FIN

AF:

0.743

Gnomad MID

AF:

0.666

Gnomad NFE

AF:

0.669

Gnomad OTH

AF:

0.691

GnomAD4 exome

AF:

0.675

AC:

20169

AN:

29878

Hom.:

6949

Cov.:

AF XY:

0.674

AC XY:

11033

AN XY:

16376

show subpopulations

African (AFR)

AF:

0.838

AC:

223

AN:

266

American (AMR)

AF:

0.600

AC:

2010

AN:

3350

Ashkenazi Jewish (ASJ)

AF:

0.703

AC:

301

AN:

428

East Asian (EAS)

AF:

0.489

AC:

639

AN:

1308

South Asian (SAS)

AF:

0.651

AC:

3313

AN:

5088

European-Finnish (FIN)

AF:

0.773

AC:

592

AN:

766

Middle Eastern (MID)

AF:

0.726

AC:

AN:

European-Non Finnish (NFE)

AF:

0.702

AC:

12187

AN:

17372

Other (OTH)

AF:

0.694

AC:

859

AN:

1238

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.534

Heterozygous variant carriers

303

605

908

1210

1513

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

160

320

480

640

800

<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:

0.710

AC:

107990

AN:

152016

Hom.:

39061

Cov.:

AF XY:

0.710

AC XY:

52745

AN XY:

74298

show subpopulations

African (AFR)

AF:

0.839

AC:

34823

AN:

41486

American (AMR)

AF:

0.652

AC:

9943

AN:

15260

Ashkenazi Jewish (ASJ)

AF:

0.641

AC:

2220

AN:

3464

East Asian (EAS)

AF:

0.482

AC:

2488

AN:

5160

South Asian (SAS)

AF:

0.617

AC:

2972

AN:

4818

European-Finnish (FIN)

AF:

0.743

AC:

7843

AN:

10552

Middle Eastern (MID)

AF:

0.664

AC:

194

AN:

292

European-Non Finnish (NFE)

AF:

0.669

AC:

45485

AN:

67964

Other (OTH)

AF:

0.695

AC:

1466

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

1558

3116

4675

6233

7791

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

828

1656

2484

3312

4140

<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:

0.706

Hom.:

3563

Bravo

AF:

0.706

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.89

CADD

Benign

0.96

(source)

DANN

Benign

0.75

PhyloP100

-0.14

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