rs2561477

Variant names:

• chr5-103273223-G-A
• rs2561477
• NM_033211.4:c.-23-2674G>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.-23-2674G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.24 in 152,088 control chromosomes in the GnomAD database, including 5,037 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 0.24 (5037 hom., cov: 32)
• Consequence: MACIR NM_033211.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.216
• Publications: 45 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=-0.85).
• 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.-23-2674G>A		intron_variant	Intron 2 of 2	ENST00000319933.7	NP_149988.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MACIR	ENST00000319933.7	c.-23-2674G>A		intron_variant	Intron 2 of 2	1	NM_033211.4	ENSP00000326110.2
MACIR	ENST00000510890.1	c.-23-2674G>A		intron_variant	Intron 2 of 2	2		ENSP00000421270.1
MACIR	ENST00000515669.5	c.-23-2674G>A		intron_variant	Intron 2 of 2	3		ENSP00000422836.1

Frequencies

GnomAD3 genomes AF: 0.240 AC: 36447 AN: 151968 Hom.: 5038 Cov.: 32

Gnomad AFR AF: 0.0979

Gnomad AMI AF: 0.275

Gnomad AMR AF: 0.230

Gnomad ASJ AF: 0.306

Gnomad EAS AF: 0.271

Gnomad SAS AF: 0.172

Gnomad FIN AF: 0.299

Gnomad MID AF: 0.283

Gnomad NFE AF: 0.317

Gnomad OTH AF: 0.254

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

GnomAD4 genome AF: 0.240 AC: 36451 AN: 152088 Hom.: 5037 Cov.: 32 AF XY: 0.237 AC XY: 17587 AN XY: 74328

African (AFR) AF: 0.0978 AC: 4060 AN: 41508

American (AMR) AF: 0.230 AC: 3512 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.306 AC: 1064 AN: 3472

East Asian (EAS) AF: 0.271 AC: 1401 AN: 5164

South Asian (SAS) AF: 0.172 AC: 829 AN: 4824

European-Finnish (FIN) AF: 0.299 AC: 3157 AN: 10554

Middle Eastern (MID) AF: 0.271 AC: 79 AN: 292

European-Non Finnish (NFE) AF: 0.317 AC: 21565 AN: 67962

Other (OTH) AF: 0.253 AC: 533 AN: 2108

Alfa AF: 0.280 Hom.: 10352

Bravo AF: 0.228

Asia WGS AF: 0.208 AC: 725 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	6.6
DANN	Benign	0.53
PhyloP100		0.22
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: rs2561477; hg19: chr5-102608924; COSMIC: COSV60635908;