2-118975372-G-T

Variant names:

• chr2-118975372-G-T
• rs1371562
• NM_006770.4:c.613+807G>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.613+807G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.329 in 152,108 control chromosomes in the GnomAD database, including 9,474 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 0.33 (9474 hom., cov: 33)
• Consequence: MARCO NM_006770.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.826
• Publications: 8 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]

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.426 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MARCO	NM_006770.4	c.613+807G>T		intron_variant	Intron 6 of 16	ENST00000327097.5	NP_006761.1
MARCO	XM_011512082.3	c.613+807G>T		intron_variant	Intron 6 of 16		XP_011510384.1
MARCO	XM_011512083.4	c.250+807G>T		intron_variant	Intron 3 of 13		XP_011510385.1
MARCO	XM_017005171.3	c.613+807G>T		intron_variant	Intron 6 of 8		XP_016860660.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MARCO	ENST00000327097.5	c.613+807G>T		intron_variant	Intron 6 of 16	1	NM_006770.4	ENSP00000318916.4

Frequencies

GnomAD3 genomes AF: 0.329 AC: 50023 AN: 151992 Hom.: 9481 Cov.: 33

Gnomad AFR AF: 0.164

Gnomad AMI AF: 0.246

Gnomad AMR AF: 0.341

Gnomad ASJ AF: 0.413

Gnomad EAS AF: 0.169

Gnomad SAS AF: 0.229

Gnomad FIN AF: 0.407

Gnomad MID AF: 0.379

Gnomad NFE AF: 0.430

Gnomad OTH AF: 0.358

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

GnomAD4 genome AF: 0.329 AC: 50014 AN: 152108 Hom.: 9474 Cov.: 33 AF XY: 0.328 AC XY: 24379 AN XY: 74344

African (AFR) AF: 0.163 AC: 6777 AN: 41506

American (AMR) AF: 0.340 AC: 5193 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.413 AC: 1430 AN: 3466

East Asian (EAS) AF: 0.169 AC: 875 AN: 5180

South Asian (SAS) AF: 0.229 AC: 1106 AN: 4824

European-Finnish (FIN) AF: 0.407 AC: 4294 AN: 10558

Middle Eastern (MID) AF: 0.387 AC: 113 AN: 292

European-Non Finnish (NFE) AF: 0.430 AC: 29256 AN: 67976

Other (OTH) AF: 0.353 AC: 746 AN: 2112

Alfa AF: 0.395 Hom.: 52011

Bravo AF: 0.317

Asia WGS AF: 0.187 AC: 652 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	2.9
DANN	Benign	0.46
PhyloP100		0.83
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: rs1371562; hg19: chr2-119732948;