10-17843910-G-T

Variant names:

• chr10-17843910-G-T
• rs525830
• NM_002438.4:c.917-1379G>T

Variant summary

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

The NM_002438.4(MRC1):​c.917-1379G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.421 in 151,908 control chromosomes in the GnomAD database, including 13,697 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 0.42 (13697 hom., cov: 31)
• Consequence: MRC1 NM_002438.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.423

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=-1.01).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.46 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MRC1	NM_002438.4	c.917-1379G>T		intron_variant	Intron 5 of 29	ENST00000569591.3	NP_002429.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MRC1	ENST00000569591.3	c.917-1379G>T		intron_variant	Intron 5 of 29	1	NM_002438.4	ENSP00000455897.1

Frequencies

GnomAD3 genomes AF: 0.421 AC: 63961 AN: 151790 Hom.: 13696 Cov.: 31

Gnomad AFR AF: 0.442

Gnomad AMI AF: 0.374

Gnomad AMR AF: 0.465

Gnomad ASJ AF: 0.394

Gnomad EAS AF: 0.476

Gnomad SAS AF: 0.426

Gnomad FIN AF: 0.484

Gnomad MID AF: 0.323

Gnomad NFE AF: 0.388

Gnomad OTH AF: 0.406

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

GnomAD4 genome AF: 0.421 AC: 63995 AN: 151908 Hom.: 13697 Cov.: 31 AF XY: 0.426 AC XY: 31592 AN XY: 74228

Gnomad4 AFR AF: 0.441

Gnomad4 AMR AF: 0.465

Gnomad4 ASJ AF: 0.394

Gnomad4 EAS AF: 0.476

Gnomad4 SAS AF: 0.426

Gnomad4 FIN AF: 0.484

Gnomad4 NFE AF: 0.388

Gnomad4 OTH AF: 0.404

Alfa AF: 0.156 Hom.: 206

Bravo AF: 0.422

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.44
DANN	Benign	0.58

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: rs525830; hg19: chr10-18132839;