chr5-103261591-G-T

Variant names:

• chr5-103261591-G-T
• rs39984
• NM_033211.4:c.-114+2695G>T

Variant summary

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

The NM_033211.4(MACIR):​c.-114+2695G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.295 in 150,510 control chromosomes in the GnomAD database, including 6,553 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 0.29 (6553 hom., cov: 30)
• Consequence: MACIR NM_033211.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.191
• Publications: 17 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=-0.99).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.314 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_033211.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MACIR	NM_033211.4	MANE Select	c.-114+2695G>T		intron	N/A	NP_149988.1	Q96GV9
	MACIR	NM_001316968.2		c.-114+1800G>T		intron	N/A	NP_001303897.1	Q96GV9
	MACIR	NM_001316969.2		c.-114+2405G>T		intron	N/A	NP_001303898.1	Q96GV9

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MACIR	ENST00000319933.7	TSL:1 MANE Select	c.-114+2695G>T		intron	N/A	ENSP00000326110.2	Q96GV9
	MACIR	ENST00000911272.1		c.-2003G>T		5_prime_UTR_premature_start_codon_gain	Exon 1 of 3	ENSP00000581331.1
	MACIR	ENST00000911273.1		c.-3342G>T		5_prime_UTR_premature_start_codon_gain	Exon 1 of 3	ENSP00000581332.1

Frequencies

GnomAD3 genomes AF: 0.295 AC: 44352 AN: 150394 Hom.: 6547 Cov.: 30

Gnomad AFR AF: 0.290

Gnomad AMI AF: 0.275

Gnomad AMR AF: 0.254

Gnomad ASJ AF: 0.301

Gnomad EAS AF: 0.264

Gnomad SAS AF: 0.172

Gnomad FIN AF: 0.299

Gnomad MID AF: 0.298

Gnomad NFE AF: 0.317

Gnomad OTH AF: 0.296

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

GnomAD4 genome AF: 0.295 AC: 44379 AN: 150510 Hom.: 6553 Cov.: 30 AF XY: 0.290 AC XY: 21335 AN XY: 73508

African (AFR) AF: 0.290 AC: 11886 AN: 40962

American (AMR) AF: 0.254 AC: 3854 AN: 15162

Ashkenazi Jewish (ASJ) AF: 0.301 AC: 1040 AN: 3456

East Asian (EAS) AF: 0.264 AC: 1346 AN: 5092

South Asian (SAS) AF: 0.171 AC: 813 AN: 4758

European-Finnish (FIN) AF: 0.299 AC: 3057 AN: 10226

Middle Eastern (MID) AF: 0.286 AC: 83 AN: 290

European-Non Finnish (NFE) AF: 0.317 AC: 21436 AN: 67568

Other (OTH) AF: 0.294 AC: 615 AN: 2092

Alfa AF: 0.306 Hom.: 932

Bravo AF: 0.291

Asia WGS AF: 0.204 AC: 700 AN: 3430

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
CADD	Benign	1.2
DANN	Benign	0.45
PhyloP100		-0.19
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: rs39984; hg19: chr5-102597292;