rs1443502

chr10-17870917-T-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_002438.4(MRC1):c.2181T>C(p.Thr727=) 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
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.63

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 -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/exons	MANE	UniProt
MRC1	NM_002438.4	c.2181T>C	p.Thr727=	synonymous_variant	14/30	ENST00000569591.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MRC1	ENST00000569591.3	c.2181T>C	p.Thr727=	synonymous_variant	14/30	1	NM_002438.4	P1

Frequencies

GnomAD3 genomes AF: 0.219 AC: 33281 AN: 152060 Hom.: 4247 Cov.: 32

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.: 0 AF XY: 0.238 AC XY: 91424 AN XY: 384308

Gnomad4 AFR exome AF: 0.128

Gnomad4 AMR exome AF: 0.119

Gnomad4 ASJ exome AF: 0.185

Gnomad4 EAS exome AF: 0.00214

Gnomad4 SAS exome AF: 0.121

Gnomad4 FIN exome AF: 0.300

Gnomad4 NFE exome AF: 0.296

Gnomad4 OTH exome AF: 0.228

GnomAD4 genome AF: 0.219 AC: 33291 AN: 152178 Hom.: 4247 Cov.: 32 AF XY: 0.216 AC XY: 16063 AN XY: 74406

Gnomad4 AFR AF: 0.129

Gnomad4 AMR AF: 0.165

Gnomad4 ASJ AF: 0.172

Gnomad4 EAS AF: 0.00482

Gnomad4 SAS AF: 0.115

Gnomad4 FIN AF: 0.297

Gnomad4 NFE AF: 0.297

Gnomad4 OTH AF: 0.200

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
Dann	Benign	0.73

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

LitVar

Other links and lift over

dbSNP: rs1443502; hg19: chr10-18159846;