2-118948829-T-G

Position:

• chr2-118948829-T-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_006770.4(MARCO):​c.97+6432T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.223 in 151,970 control chromosomes in the GnomAD database, including 5,732 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 0.22 (5732 hom., cov: 33)
• Consequence: MARCO NM_006770.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.879

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=-1.02).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.464 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MARCO	NM_006770.4	c.97+6432T>G		intron_variant		ENST00000327097.5	NP_006761.1
MARCO	XM_011512082.3	c.97+6432T>G		intron_variant			XP_011510384.1
MARCO	XM_011512083.4	c.97+6432T>G		intron_variant			XP_011510385.1
MARCO	XM_017005171.3	c.97+6432T>G		intron_variant			XP_016860660.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MARCO	ENST00000327097.5	c.97+6432T>G		intron_variant		1	NM_006770.4	ENSP00000318916	P1
MARCO	ENST00000412481.1	c.-138+3904T>G		intron_variant		4		ENSP00000409192

Frequencies

GnomAD3 genomes AF: 0.223 AC: 33918 AN: 151852 Hom.: 5725 Cov.: 33

Gnomad AFR AF: 0.470

Gnomad AMI AF: 0.104

Gnomad AMR AF: 0.116

Gnomad ASJ AF: 0.112

Gnomad EAS AF: 0.220

Gnomad SAS AF: 0.307

Gnomad FIN AF: 0.155

Gnomad MID AF: 0.155

Gnomad NFE AF: 0.112

Gnomad OTH AF: 0.187

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

GnomAD4 genome AF: 0.223 AC: 33958 AN: 151970 Hom.: 5732 Cov.: 33 AF XY: 0.226 AC XY: 16765 AN XY: 74320

Gnomad4 AFR AF: 0.470

Gnomad4 AMR AF: 0.116

Gnomad4 ASJ AF: 0.112

Gnomad4 EAS AF: 0.220

Gnomad4 SAS AF: 0.306

Gnomad4 FIN AF: 0.155

Gnomad4 NFE AF: 0.112

Gnomad4 OTH AF: 0.190

Alfa AF: 0.152 Hom.: 527

Bravo AF: 0.228

Asia WGS AF: 0.236 AC: 819 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.64
DANN	Benign	0.33

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: rs6752783; hg19: chr2-119706405;