rs434816

Positions:

• chr5-103263627-A-G

Variant summary

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

The NM_033211.4(MACIR):​c.-113-2281A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.284 in 152,090 control chromosomes in the GnomAD database, including 6,210 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 0.28 (6210 hom., cov: 33)
• Consequence: MACIR NM_033211.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.721

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

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• 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/exons	MANE	Protein	UniProt
MACIR	NM_033211.4	c.-113-2281A>G		intron_variant		ENST00000319933.7	NP_149988.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MACIR	ENST00000319933.7	c.-113-2281A>G		intron_variant		1	NM_033211.4	ENSP00000326110.2
MACIR	ENST00000510890.1	c.-113-2281A>G		intron_variant		2		ENSP00000421270.1
MACIR	ENST00000515669.5	c.-113-2281A>G		intron_variant		3		ENSP00000422836.1

Frequencies

GnomAD3 genomes AF: 0.284 AC: 43155 AN: 151972 Hom.: 6205 Cov.: 33

Gnomad AFR AF: 0.251

Gnomad AMI AF: 0.274

Gnomad AMR AF: 0.252

Gnomad ASJ AF: 0.302

Gnomad EAS AF: 0.270

Gnomad SAS AF: 0.172

Gnomad FIN AF: 0.298

Gnomad MID AF: 0.290

Gnomad NFE AF: 0.317

Gnomad OTH AF: 0.285

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

GnomAD4 genome AF: 0.284 AC: 43177 AN: 152090 Hom.: 6210 Cov.: 33 AF XY: 0.280 AC XY: 20807 AN XY: 74370

Gnomad4 AFR AF: 0.251

Gnomad4 AMR AF: 0.252

Gnomad4 ASJ AF: 0.302

Gnomad4 EAS AF: 0.271

Gnomad4 SAS AF: 0.171

Gnomad4 FIN AF: 0.298

Gnomad4 NFE AF: 0.317

Gnomad4 OTH AF: 0.283

Alfa AF: 0.301 Hom.: 877

Bravo AF: 0.278

Asia WGS AF: 0.217 AC: 753 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	6.4
DANN	Benign	0.82

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: rs434816; hg19: chr5-102599328;