rs2255672

Positions:

• chr18-50806997-T-C

Variant summary

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

The NM_031939.6(MRO):​c.100-147A>G 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 769,198 control chromosomes in the GnomAD database, including 24,995 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 0.20 (3684 hom., cov: 31)
  • Exomes 𝑓: 0.25 (21311 hom.)
• Consequence: MRO NM_031939.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.180

Genes affected

MRO (HGNC:24121): (maestro) This gene is specifically transcribed in males before and after differentiation of testis, and the encoded protein may play an important role in a mammalian sex determination. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.28 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MRO	NM_031939.6	c.100-147A>G		intron_variant		ENST00000398439.8	NP_114145.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MRO	ENST00000398439.8	c.100-147A>G		intron_variant		1	NM_031939.6	ENSP00000381465	P1

Frequencies

GnomAD3 genomes AF: 0.198 AC: 30105 AN: 151968 Hom.: 3679 Cov.: 31

Gnomad AFR AF: 0.0806

Gnomad AMI AF: 0.239

Gnomad AMR AF: 0.137

Gnomad ASJ AF: 0.198

Gnomad EAS AF: 0.0874

Gnomad SAS AF: 0.216

Gnomad FIN AF: 0.245

Gnomad MID AF: 0.142

Gnomad NFE AF: 0.284

Gnomad OTH AF: 0.176

GnomAD4 exome AF: 0.251 AC: 154625 AN: 617112 Hom.: 21311 AF XY: 0.250 AC XY: 80594 AN XY: 322376

Gnomad4 AFR exome AF: 0.0789

Gnomad4 AMR exome AF: 0.111

Gnomad4 ASJ exome AF: 0.196

Gnomad4 EAS exome AF: 0.0891

Gnomad4 SAS exome AF: 0.219

Gnomad4 FIN exome AF: 0.246

Gnomad4 NFE exome AF: 0.287

Gnomad4 OTH exome AF: 0.227

GnomAD4 genome AF: 0.198 AC: 30132 AN: 152086 Hom.: 3684 Cov.: 31 AF XY: 0.193 AC XY: 14327 AN XY: 74336

Gnomad4 AFR AF: 0.0808

Gnomad4 AMR AF: 0.136

Gnomad4 ASJ AF: 0.198

Gnomad4 EAS AF: 0.0876

Gnomad4 SAS AF: 0.217

Gnomad4 FIN AF: 0.245

Gnomad4 NFE AF: 0.284

Gnomad4 OTH AF: 0.180

Alfa AF: 0.249 Hom.: 3060

Bravo AF: 0.180

Asia WGS AF: 0.178 AC: 619 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	2.1
DANN	Benign	0.76

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: rs2255672; hg19: chr18-48333367;