2-118942520-T-C

Position:

• chr2-118942520-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.97+123T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.616 in 711,290 control chromosomes in the GnomAD database, including 137,373 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 0.62 (29058 hom., cov: 33)
  • Exomes 𝑓: 0.62 (108315 hom.)
• Consequence: MARCO NM_006770.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.698

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=-0.9).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.634 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MARCO	NM_006770.4	c.97+123T>C		intron_variant		ENST00000327097.5	NP_006761.1
MARCO	XM_011512082.3	c.97+123T>C		intron_variant			XP_011510384.1
MARCO	XM_011512083.4	c.97+123T>C		intron_variant			XP_011510385.1
MARCO	XM_017005171.3	c.97+123T>C		intron_variant			XP_016860660.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MARCO	ENST00000327097.5	c.97+123T>C		intron_variant		1	NM_006770.4	ENSP00000318916.4
MARCO	ENST00000412481.1	c.-271+123T>C		intron_variant		4		ENSP00000409192.1

Frequencies

GnomAD3 genomes AF: 0.616 AC: 93599 AN: 151982 Hom.: 29042 Cov.: 33

Gnomad AFR AF: 0.594

Gnomad AMI AF: 0.523

Gnomad AMR AF: 0.638

Gnomad ASJ AF: 0.703

Gnomad EAS AF: 0.638

Gnomad SAS AF: 0.426

Gnomad FIN AF: 0.569

Gnomad MID AF: 0.650

Gnomad NFE AF: 0.639

Gnomad OTH AF: 0.633

GnomAD4 exome AF: 0.616 AC: 344508 AN: 559190 Hom.: 108315 AF XY: 0.606 AC XY: 178920 AN XY: 295254

Gnomad4 AFR exome AF: 0.600

Gnomad4 AMR exome AF: 0.636

Gnomad4 ASJ exome AF: 0.706

Gnomad4 EAS exome AF: 0.631

Gnomad4 SAS exome AF: 0.413

Gnomad4 FIN exome AF: 0.583

Gnomad4 NFE exome AF: 0.644

Gnomad4 OTH exome AF: 0.630

GnomAD4 genome AF: 0.616 AC: 93658 AN: 152100 Hom.: 29058 Cov.: 33 AF XY: 0.610 AC XY: 45352 AN XY: 74358

Gnomad4 AFR AF: 0.594

Gnomad4 AMR AF: 0.637

Gnomad4 ASJ AF: 0.703

Gnomad4 EAS AF: 0.637

Gnomad4 SAS AF: 0.425

Gnomad4 FIN AF: 0.569

Gnomad4 NFE AF: 0.639

Gnomad4 OTH AF: 0.632

Alfa AF: 0.621 Hom.: 13536

Bravo AF: 0.627

Asia WGS AF: 0.510 AC: 1771 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	1.4
DANN	Benign	0.47

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: rs2077344; hg19: chr2-119700096; COSMIC: COSV59055190;