rs4476230

Positions:

• chr17-55393744-T-G

Variant summary

Our verdict is Benign. Variant got -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

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

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MMD	NM_012329.3	c.*590A>C		3_prime_UTR_variant	7/7	ENST00000262065.8	NP_036461.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MMD	ENST00000262065.8	c.*590A>C		3_prime_UTR_variant	7/7	1	NM_012329.3	ENSP00000262065	P1
MMD	ENST00000649377.1	c.*590A>C		3_prime_UTR_variant	8/8			ENSP00000497849

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

Gnomad4 FIN exome AF: 0.353

Gnomad4 NFE exome AF: 0.500

Gnomad4 OTH exome AF: 0.750

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

Gnomad4 AFR AF: 0.0947

Gnomad4 AMR AF: 0.384

Gnomad4 ASJ AF: 0.339

Gnomad4 EAS AF: 0.156

Gnomad4 SAS AF: 0.199

Gnomad4 FIN AF: 0.375

Gnomad4 NFE AF: 0.418

Gnomad4 OTH AF: 0.304

Alfa AF: 0.384 Hom.: 11100

Bravo AF: 0.299

Asia WGS AF: 0.232 AC: 809 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	14
DANN	Benign	0.83

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: rs4476230; hg19: chr17-53471105; COSMIC: COSV50435002;