rs2477664

Positions:

• chr10-17833817-T-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.780T>A​(p.Ile260=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.494 in 780,750 control chromosomes in the GnomAD database, including 97,037 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 0.49 (18445 hom., cov: 33)
  • Exomes 𝑓: 0.50 (78592 hom.)
• Consequence: MRC1 NM_002438.4 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.84

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=-0.66).
• BP7: Synonymous conserved (PhyloP=-2.84 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.535 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MRC1	NM_002438.4	c.780T>A	p.Ile260=	synonymous_variant	4/30	ENST00000569591.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MRC1	ENST00000569591.3	c.780T>A	p.Ile260=	synonymous_variant	4/30	1	NM_002438.4	P1

Frequencies

GnomAD3 genomes AF: 0.490 AC: 74401 AN: 151860 Hom.: 18440 Cov.: 33

Gnomad AFR AF: 0.438

Gnomad AMI AF: 0.591

Gnomad AMR AF: 0.466

Gnomad ASJ AF: 0.523

Gnomad EAS AF: 0.441

Gnomad SAS AF: 0.400

Gnomad FIN AF: 0.453

Gnomad MID AF: 0.462

Gnomad NFE AF: 0.539

Gnomad OTH AF: 0.495

GnomAD3 exomes AF: 0.000450 AC: 84 AN: 186574 Hom.: 22 AF XY: 0.000525 AC XY: 53 AN XY: 101046

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.000146

Gnomad ASJ exome AF: 0.000705

Gnomad EAS exome AF: 0.000768

Gnomad SAS exome AF: 0.000158

Gnomad FIN exome AF: 0.000699

Gnomad NFE exome AF: 0.000567

Gnomad OTH exome AF: 0.000875

GnomAD4 exome AF: 0.495 AC: 311455 AN: 628772 Hom.: 78592 Cov.: 0 AF XY: 0.492 AC XY: 168519 AN XY: 342530

Gnomad4 AFR exome AF: 0.440

Gnomad4 AMR exome AF: 0.440

Gnomad4 ASJ exome AF: 0.523

Gnomad4 EAS exome AF: 0.445

Gnomad4 SAS exome AF: 0.389

Gnomad4 FIN exome AF: 0.458

Gnomad4 NFE exome AF: 0.535

Gnomad4 OTH exome AF: 0.500

GnomAD4 genome AF: 0.490 AC: 74438 AN: 151978 Hom.: 18445 Cov.: 33 AF XY: 0.485 AC XY: 36057 AN XY: 74278

Gnomad4 AFR AF: 0.438

Gnomad4 AMR AF: 0.466

Gnomad4 ASJ AF: 0.523

Gnomad4 EAS AF: 0.441

Gnomad4 SAS AF: 0.399

Gnomad4 FIN AF: 0.453

Gnomad4 NFE AF: 0.539

Gnomad4 OTH AF: 0.496

Alfa AF: 0.495 Hom.: 1801

Bravo AF: 0.487

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.66
CADD	Benign	0.41
DANN	Benign	0.76

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: rs2477664; hg19: chr10-17875816; COSMIC: COSV58888652;