chr2-118983428-C-T

Variant names:

• chr2-118983428-C-T
• rs6751745
• NM_006770.4:c.1063+1018C>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.1063+1018C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.307 in 152,022 control chromosomes in the GnomAD database, including 9,707 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 0.31 (9707 hom., cov: 32)
• Consequence: MARCO NM_006770.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.499
• Publications: 13 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=-0.93).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.576 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MARCO	NM_006770.4	c.1063+1018C>T		intron_variant	Intron 12 of 16	ENST00000327097.5	NP_006761.1
MARCO	XM_011512082.3	c.1063+1018C>T		intron_variant	Intron 12 of 16		XP_011510384.1
MARCO	XM_011512083.4	c.700+1018C>T		intron_variant	Intron 9 of 13		XP_011510385.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MARCO	ENST00000327097.5	c.1063+1018C>T		intron_variant	Intron 12 of 16	1	NM_006770.4	ENSP00000318916.4

Frequencies

GnomAD3 genomes AF: 0.307 AC: 46649 AN: 151904 Hom.: 9668 Cov.: 32

Gnomad AFR AF: 0.582

Gnomad AMI AF: 0.120

Gnomad AMR AF: 0.249

Gnomad ASJ AF: 0.241

Gnomad EAS AF: 0.318

Gnomad SAS AF: 0.435

Gnomad FIN AF: 0.159

Gnomad MID AF: 0.272

Gnomad NFE AF: 0.174

Gnomad OTH AF: 0.271

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

GnomAD4 genome AF: 0.307 AC: 46746 AN: 152022 Hom.: 9707 Cov.: 32 AF XY: 0.308 AC XY: 22867 AN XY: 74328

African (AFR) AF: 0.582 AC: 24103 AN: 41402

American (AMR) AF: 0.250 AC: 3813 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.241 AC: 836 AN: 3472

East Asian (EAS) AF: 0.318 AC: 1639 AN: 5152

South Asian (SAS) AF: 0.434 AC: 2089 AN: 4818

European-Finnish (FIN) AF: 0.159 AC: 1681 AN: 10598

Middle Eastern (MID) AF: 0.279 AC: 82 AN: 294

European-Non Finnish (NFE) AF: 0.174 AC: 11811 AN: 67988

Other (OTH) AF: 0.276 AC: 583 AN: 2112

Alfa AF: 0.237 Hom.: 9941

Bravo AF: 0.324

Asia WGS AF: 0.397 AC: 1380 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	4.5
DANN	Benign	0.58
PhyloP100		0.50
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: rs6751745; hg19: chr2-119741004;