10-17849727-C-T

Variant names:

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

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

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
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -3.38

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

Verdict is Benign. Variant got -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	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	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.: 31

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

GnomAD3 exomes AF: 0.0000825 AC: 6 AN: 72704 Hom.: 2 AF XY: 0.0000503 AC XY: 2 AN XY: 39762

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 SAS exome AF: 0.000289

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.: 0 AF XY: 0.810 AC XY: 277530 AN XY: 342490

Gnomad4 AFR exome AF: 0.635

Gnomad4 AMR exome AF: 0.866

Gnomad4 ASJ exome AF: 0.830

Gnomad4 EAS exome AF: 0.809

Gnomad4 SAS exome AF: 0.859

Gnomad4 FIN exome AF: 0.873

Gnomad4 NFE exome AF: 0.790

Gnomad4 OTH exome AF: 0.793

GnomAD4 genome AF: 0.757 AC: 114964 AN: 151814 Hom.: 44052 Cov.: 31 AF XY: 0.763 AC XY: 56638 AN XY: 74188

Gnomad4 AFR AF: 0.635

Gnomad4 AMR AF: 0.807

Gnomad4 ASJ AF: 0.834

Gnomad4 EAS AF: 0.828

Gnomad4 SAS AF: 0.867

Gnomad4 FIN AF: 0.871

Gnomad4 NFE AF: 0.786

Gnomad4 OTH AF: 0.768

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
DANN	Benign	0.73

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

LitVar

Other links and lift over

dbSNP: rs71497224; hg19: chr10-18138656; COSMIC: COSV99519408; COSMIC: COSV99519408;