rs2253120

Positions:

• chr10-17823255-G-A

Variant summary

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

The NM_002438.4(MRC1):​c.243G>A​(p.Thr81=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.317 in 780,544 control chromosomes in the GnomAD database, including 40,079 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 0.32 (7736 hom., cov: 32)
  • Exomes 𝑓: 0.32 (32343 hom.)
• Consequence: MRC1 NM_002438.4 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -3.87

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=-0.84).
• BP7: Synonymous conserved (PhyloP=-3.87 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.329 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MRC1	NM_002438.4	c.243G>A	p.Thr81=	synonymous_variant	2/30	ENST00000569591.3	NP_002429.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MRC1	ENST00000569591.3	c.243G>A	p.Thr81=	synonymous_variant	2/30	1	NM_002438.4	ENSP00000455897	P1

Frequencies

GnomAD3 genomes AF: 0.318 AC: 48292 AN: 151866 Hom.: 7730 Cov.: 32

Gnomad AFR AF: 0.313

Gnomad AMI AF: 0.254

Gnomad AMR AF: 0.324

Gnomad ASJ AF: 0.332

Gnomad EAS AF: 0.228

Gnomad SAS AF: 0.321

Gnomad FIN AF: 0.275

Gnomad MID AF: 0.282

Gnomad NFE AF: 0.333

Gnomad OTH AF: 0.319

GnomAD4 exome AF: 0.317 AC: 199480 AN: 628560 Hom.: 32343 Cov.: 0 AF XY: 0.317 AC XY: 108689 AN XY: 342430

Gnomad4 AFR exome AF: 0.314

Gnomad4 AMR exome AF: 0.340

Gnomad4 ASJ exome AF: 0.329

Gnomad4 EAS exome AF: 0.240

Gnomad4 SAS exome AF: 0.318

Gnomad4 FIN exome AF: 0.279

Gnomad4 NFE exome AF: 0.329

Gnomad4 OTH exome AF: 0.311

GnomAD4 genome AF: 0.318 AC: 48318 AN: 151984 Hom.: 7736 Cov.: 32 AF XY: 0.317 AC XY: 23521 AN XY: 74268

Gnomad4 AFR AF: 0.313

Gnomad4 AMR AF: 0.325

Gnomad4 ASJ AF: 0.332

Gnomad4 EAS AF: 0.229

Gnomad4 SAS AF: 0.321

Gnomad4 FIN AF: 0.275

Gnomad4 NFE AF: 0.333

Gnomad4 OTH AF: 0.314

Alfa AF: 0.321 Hom.: 744

Bravo AF: 0.318

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	0.0030
DANN	Benign	0.74

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: rs2253120; hg19: chr10-17865254;