rs12987402

Positions:

• chr2-118991220-C-T

Variant summary

Our verdict is Benign. Variant got -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

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

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MARCO	NM_006770.4	c.1109-557C>T		intron_variant		ENST00000327097.5	NP_006761.1
MARCO	XM_011512082.3	c.1103-551C>T		intron_variant			XP_011510384.1
MARCO	XM_011512083.4	c.746-557C>T		intron_variant			XP_011510385.1
LOC124906072	XR_007087213.1	n.249-54G>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MARCO	ENST00000327097.5	c.1109-557C>T		intron_variant		1	NM_006770.4	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

Gnomad4 AFR AF: 0.388

Gnomad4 AMR AF: 0.572

Gnomad4 ASJ AF: 0.616

Gnomad4 EAS AF: 0.383

Gnomad4 SAS AF: 0.532

Gnomad4 FIN AF: 0.633

Gnomad4 NFE AF: 0.618

Gnomad4 OTH AF: 0.553

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 v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	2.8
DANN	Benign	0.66

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: rs12987402; hg19: chr2-119748796;