rs2288786

Variant names:

• chr5-103265053-G-A
• rs2288786
• NM_033211.4:c.-113-855G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_033211.4(MACIR):​c.-113-855G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.249 in 151,926 control chromosomes in the GnomAD database, including 5,189 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 0.25 (5189 hom., cov: 32)
• Consequence: MACIR NM_033211.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.141
• Publications: 15 publications found

Genes affected

MACIR (HGNC:25052): (macrophage immunometabolism regulator) This gene, MACIR (previously known as C5orf30), has been associated with rheumatoid arthritis, functioning as a negative regulator of tissue damage and modulating the activity of synovial fibroblasts and macrophages. The encoded protein is highly conserved in vertebrate genomes but has no significant similarity to any other human protein. [provided by RefSeq, Dec 2019]

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.75).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.314 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MACIR	NM_033211.4	c.-113-855G>A		intron_variant	Intron 1 of 2	ENST00000319933.7	NP_149988.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MACIR	ENST00000319933.7	c.-113-855G>A		intron_variant	Intron 1 of 2	1	NM_033211.4	ENSP00000326110.2
MACIR	ENST00000510890.1	c.-113-855G>A		intron_variant	Intron 1 of 2	2		ENSP00000421270.1
MACIR	ENST00000515669.5	c.-113-855G>A		intron_variant	Intron 1 of 2	3		ENSP00000422836.1

Frequencies

GnomAD3 genomes AF: 0.249 AC: 37798 AN: 151806 Hom.: 5188 Cov.: 32

Gnomad AFR AF: 0.131

Gnomad AMI AF: 0.273

Gnomad AMR AF: 0.231

Gnomad ASJ AF: 0.300

Gnomad EAS AF: 0.270

Gnomad SAS AF: 0.173

Gnomad FIN AF: 0.300

Gnomad MID AF: 0.280

Gnomad NFE AF: 0.317

Gnomad OTH AF: 0.257

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

GnomAD4 genome AF: 0.249 AC: 37810 AN: 151926 Hom.: 5189 Cov.: 32 AF XY: 0.245 AC XY: 18228 AN XY: 74252

African (AFR) AF: 0.131 AC: 5431 AN: 41464

American (AMR) AF: 0.231 AC: 3530 AN: 15256

Ashkenazi Jewish (ASJ) AF: 0.300 AC: 1039 AN: 3466

East Asian (EAS) AF: 0.271 AC: 1394 AN: 5152

South Asian (SAS) AF: 0.173 AC: 832 AN: 4822

European-Finnish (FIN) AF: 0.300 AC: 3161 AN: 10546

Middle Eastern (MID) AF: 0.265 AC: 78 AN: 294

European-Non Finnish (NFE) AF: 0.317 AC: 21556 AN: 67904

Other (OTH) AF: 0.256 AC: 541 AN: 2114

Alfa AF: 0.290 Hom.: 6418

Bravo AF: 0.239

Asia WGS AF: 0.214 AC: 743 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.75
CADD	Benign	7.0
DANN	Benign	0.72
PhyloP100		-0.14
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: rs2288786; hg19: chr5-102600754;