rs2947600

chr10-17817451-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.62-5623T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.742 in 151,968 control chromosomes in the GnomAD database, including 43,062 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 0.74 (43062 hom., cov: 30)
• Consequence: MRC1 NM_002438.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.686

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=-0.95).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.92 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MRC1	NM_002438.4	c.62-5623T>C		intron_variant		ENST00000569591.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MRC1	ENST00000569591.3	c.62-5623T>C		intron_variant		1	NM_002438.4	P1

Frequencies

GnomAD3 genomes AF: 0.742 AC: 112726 AN: 151850 Hom.: 43015 Cov.: 30

Gnomad AFR AF: 0.928

Gnomad AMI AF: 0.683

Gnomad AMR AF: 0.637

Gnomad ASJ AF: 0.702

Gnomad EAS AF: 0.624

Gnomad SAS AF: 0.690

Gnomad FIN AF: 0.628

Gnomad MID AF: 0.750

Gnomad NFE AF: 0.687

Gnomad OTH AF: 0.735

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.742 AC: 112836 AN: 151968 Hom.: 43062 Cov.: 30 AF XY: 0.738 AC XY: 54828 AN XY: 74278

Gnomad4 AFR AF: 0.928

Gnomad4 AMR AF: 0.637

Gnomad4 ASJ AF: 0.702

Gnomad4 EAS AF: 0.625

Gnomad4 SAS AF: 0.689

Gnomad4 FIN AF: 0.628

Gnomad4 NFE AF: 0.687

Gnomad4 OTH AF: 0.733

Alfa AF: 0.734 Hom.: 3851

Bravo AF: 0.750

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
Cadd	Benign	2.5
Dann	Benign	0.49

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: rs2947600; hg19: chr10-17859450;