rs71497224

Variant names:

• chr10-17849727-C-G
• rs71497224
• NM_002438.4:c.1212C>G

Your query was ambiguous. Multiple possible variants found:

• chr10-17849727-C-G
• chr10-17849727-C-T

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_002438.4(MRC1):​c.1212C>G​(p.Ile404Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000659 in 151,762 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.0000066 (0 hom., cov: 31)
• Consequence: MRC1 NM_002438.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -3.38
• Publications: 7 publications found

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]

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.16836971).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002438.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MRC1	NM_002438.4	MANE Select	c.1212C>G	p.Ile404Met	missense	Exon 7 of 30	NP_002429.1	P22897-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MRC1	ENST00000569591.3	TSL:1 MANE Select	c.1212C>G	p.Ile404Met	missense	Exon 7 of 30	ENSP00000455897.1	P22897-1
	MRC1	ENST00000954013.1		c.1098C>G	p.Ile366Met	missense	Exon 6 of 29	ENSP00000624072.1
	MRC1	ENST00000884128.1		c.1038C>G	p.Ile346Met	missense	Exon 6 of 29	ENSP00000554187.1

Frequencies

GnomAD3 genomes AF: 0.00000659 AC: 1 AN: 151762 Hom.: 0 Cov.: 31

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000147

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000275 AC: 2 AN: 72704 AF XY: 0.00

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000477

Gnomad OTH exome AF: 0.00

GnomAD4 exome Cov.: 0

GnomAD4 genome AF: 0.00000659 AC: 1 AN: 151762 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 74092

African (AFR) AF: 0.00 AC: 0 AN: 41304

American (AMR) AF: 0.00 AC: 0 AN: 15236

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5170

South Asian (SAS) AF: 0.00 AC: 0 AN: 4810

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10540

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.0000147 AC: 1 AN: 67924

Other (OTH) AF: 0.00 AC: 0 AN: 2086

Alfa AF: 0.00 Hom.: 643

ExAC AF: 0.0000399 AC: 2

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.079
BayesDel_addAF	Benign	-0.30	T
BayesDel_noAF	Benign	-0.66
CADD	Benign	0.011
DANN	Uncertain	0.99
DEOGEN2	Benign	0.058	T
Eigen	Benign	-0.78
Eigen_PC	Benign	-0.94
FATHMM_MKL	Benign	0.019	N
LIST_S2	Benign	0.84	T
M_CAP	Benign	0.022	T
MetaRNN	Benign	0.17	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.90	L
PhyloP100		-3.4
PrimateAI	Benign	0.43	T
PROVEAN	Benign	-1.1	N
Sift	Uncertain	0.021	D
Sift4G	Uncertain	0.032	D
Polyphen		0.99	D
Vest4		0.29
MutPred		0.40		Gain of disorder (P = 0.076)
MVP		0.068
ClinPred		0.57	D
GERP RS		-5.2
Varity_R		0.42
gMVP		0.33
Mutation Taster		=99/1	polymorphism

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

Other links and lift over

dbSNP: rs71497224; hg19: chr10-18138656;