chr2-118991220-C-T

Variant names:

• chr2-118991220-C-T
• rs12987402
• NM_006770.4:c.1109-557C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_006770.4(MARCO):​c.1109-557C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.538 in 151,288 control chromosomes in the GnomAD database, including 22,755 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 0.54 (22755 hom., cov: 29)
• Consequence: MARCO NM_006770.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.789
• Publications: 7 publications found

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]

LOC124906072 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.613 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_006770.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MARCO	NM_006770.4	MANE Select	c.1109-557C>T		intron	N/A	NP_006761.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MARCO	ENST00000327097.5	TSL:1 MANE Select	c.1109-557C>T		intron	N/A	ENSP00000318916.4

Frequencies

GnomAD3 genomes AF: 0.538 AC: 81346 AN: 151174 Hom.: 22734 Cov.: 29

Gnomad AFR AF: 0.388

Gnomad AMI AF: 0.373

Gnomad AMR AF: 0.572

Gnomad ASJ AF: 0.616

Gnomad EAS AF: 0.383

Gnomad SAS AF: 0.529

Gnomad FIN AF: 0.633

Gnomad MID AF: 0.500

Gnomad NFE AF: 0.618

Gnomad OTH AF: 0.550

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

GnomAD4 genome AF: 0.538 AC: 81405 AN: 151288 Hom.: 22755 Cov.: 29 AF XY: 0.538 AC XY: 39696 AN XY: 73806

African (AFR) AF: 0.388 AC: 15985 AN: 41244

American (AMR) AF: 0.572 AC: 8698 AN: 15204

Ashkenazi Jewish (ASJ) AF: 0.616 AC: 2135 AN: 3466

East Asian (EAS) AF: 0.383 AC: 1964 AN: 5134

South Asian (SAS) AF: 0.532 AC: 2551 AN: 4794

European-Finnish (FIN) AF: 0.633 AC: 6510 AN: 10278

Middle Eastern (MID) AF: 0.510 AC: 149 AN: 292

European-Non Finnish (NFE) AF: 0.618 AC: 41912 AN: 67868

Other (OTH) AF: 0.553 AC: 1162 AN: 2100

Alfa AF: 0.575 Hom.: 4056

Bravo AF: 0.528

Asia WGS AF: 0.455 AC: 1583 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	2.8
DANN	Benign	0.66
PhyloP100		-0.79
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs12987402; hg19: chr2-119748796;