rs4476230

Variant names:

• chr17-55393744-T-G
• rs4476230
• NM_012329.3:c.*590A>C

Variant summary

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

The NM_012329.3(MMD):​c.*590A>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.304 in 152,522 control chromosomes in the GnomAD database, including 8,682 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 0.30 (8653 hom., cov: 33)
  • Exomes 𝑓: 0.36 (29 hom.)
• Consequence: MMD NM_012329.3 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.437
• Publications: 12 publications found

Genes affected

MMD (HGNC:7153): (monocyte to macrophage differentiation associated) This protein is expressed by in vitro differentiated macrophages but not freshly isolated monocytes. Although sequence analysis identifies seven potential transmembrane domains, this protein has little homology to G-protein receptors and it has not been positively identified as a receptor. A suggested alternative function is that of an ion channel protein in maturing macrophages. [provided by RefSeq, Jul 2008]

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 = 0.414 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_012329.3. 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
	MMD	NM_012329.3	MANE Select	c.*590A>C		3_prime_UTR	Exon 7 of 7	NP_036461.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MMD	ENST00000262065.8	TSL:1 MANE Select	c.*590A>C		3_prime_UTR	Exon 7 of 7	ENSP00000262065.3	Q15546
	MMD	ENST00000649377.1		c.*590A>C		3_prime_UTR	Exon 8 of 8	ENSP00000497849.1	A0A3B3ITQ3
	MMD	ENST00000936217.1		c.*590A>C		3_prime_UTR	Exon 7 of 7	ENSP00000606276.1

Frequencies

GnomAD3 genomes AF: 0.304 AC: 46220 AN: 151976 Hom.: 8635 Cov.: 33

Gnomad AFR AF: 0.0949

Gnomad AMI AF: 0.482

Gnomad AMR AF: 0.384

Gnomad ASJ AF: 0.339

Gnomad EAS AF: 0.156

Gnomad SAS AF: 0.197

Gnomad FIN AF: 0.375

Gnomad MID AF: 0.250

Gnomad NFE AF: 0.418

Gnomad OTH AF: 0.295

GnomAD4 exome AF: 0.357 AC: 153 AN: 428 Hom.: 29 Cov.: 0 AF XY: 0.337 AC XY: 87 AN XY: 258

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AF: 0.353 AC: 149 AN: 422

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.500 AC: 1 AN: 2

Other (OTH) AF: 0.750 AC: 3 AN: 4

GnomAD4 genome AF: 0.304 AC: 46259 AN: 152094 Hom.: 8653 Cov.: 33 AF XY: 0.300 AC XY: 22334 AN XY: 74338

African (AFR) AF: 0.0947 AC: 3932 AN: 41534

American (AMR) AF: 0.384 AC: 5867 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.339 AC: 1176 AN: 3472

East Asian (EAS) AF: 0.156 AC: 808 AN: 5182

South Asian (SAS) AF: 0.199 AC: 958 AN: 4814

European-Finnish (FIN) AF: 0.375 AC: 3951 AN: 10532

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

European-Non Finnish (NFE) AF: 0.418 AC: 28409 AN: 67970

Other (OTH) AF: 0.304 AC: 642 AN: 2114

Alfa AF: 0.374 Hom.: 14118

Bravo AF: 0.299

Asia WGS AF: 0.232 AC: 809 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.75
CADD	Benign	14
DANN	Benign	0.83
PhyloP100		0.44
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: rs4476230; hg19: chr17-53471105; COSMIC: COSV50435002;