rs11685286

Positions:

• chr2-118993752-T-C

Variant summary

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

The NM_006770.4(MARCO):​c.1429+452T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.132 in 152,122 control chromosomes in the GnomAD database, including 1,648 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 0.13 (1648 hom., cov: 32)
• Consequence: MARCO NM_006770.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.105

Genes affected

MARCO (HGNC:6895): (macrophage receptor with collagenous structure) The protein encoded by this gene is a member of the class A scavenger receptor family and is part of the innate antimicrobial immune system. The protein may bind both Gram-negative and Gram-positive bacteria via an extracellular, C-terminal, scavenger receptor cysteine-rich (SRCR) domain. In addition to short cytoplasmic and transmembrane domains, there is an extracellular spacer domain and a long, extracellular collagenous domain. The protein may form a trimeric molecule by the association of the collagenous domains of three identical polypeptide chains. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.219 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MARCO	NM_006770.4	c.1429+452T>C		intron_variant		ENST00000327097.5
MARCO	XM_011512082.3	c.1429+452T>C		intron_variant
MARCO	XM_011512083.4	c.1066+452T>C		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MARCO	ENST00000327097.5	c.1429+452T>C		intron_variant		1	NM_006770.4	P1
MARCO	ENST00000494979.1	n.284+452T>C		intron_variant, non_coding_transcript_variant		2

Frequencies

GnomAD3 genomes AF: 0.132 AC: 20045 AN: 152004 Hom.: 1643 Cov.: 32

Gnomad AFR AF: 0.0398

Gnomad AMI AF: 0.101

Gnomad AMR AF: 0.210

Gnomad ASJ AF: 0.132

Gnomad EAS AF: 0.114

Gnomad SAS AF: 0.228

Gnomad FIN AF: 0.225

Gnomad MID AF: 0.127

Gnomad NFE AF: 0.151

Gnomad OTH AF: 0.136

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

GnomAD4 genome AF: 0.132 AC: 20071 AN: 152122 Hom.: 1648 Cov.: 32 AF XY: 0.138 AC XY: 10271 AN XY: 74368

Gnomad4 AFR AF: 0.0397

Gnomad4 AMR AF: 0.211

Gnomad4 ASJ AF: 0.132

Gnomad4 EAS AF: 0.114

Gnomad4 SAS AF: 0.230

Gnomad4 FIN AF: 0.225

Gnomad4 NFE AF: 0.151

Gnomad4 OTH AF: 0.137

Alfa AF: 0.144 Hom.: 299

Bravo AF: 0.123

Asia WGS AF: 0.132 AC: 461 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	4.0
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: rs11685286; hg19: chr2-119751328;