18-50806997-T-C

Variant names:

• chr18-50806997-T-C
• rs2255672
• NM_031939.6:c.100-147A>G

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 5 publications found

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

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_031939.6. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MRO	NM_031939.6	MANE Select	c.100-147A>G		intron	N/A	NP_114145.2
	MRO	NM_001127176.3		c.142-147A>G		intron	N/A	NP_001120648.1
	MRO	NM_001369508.2		c.100-147A>G		intron	N/A	NP_001356437.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MRO	ENST00000398439.8	TSL:1 MANE Select	c.100-147A>G		intron	N/A	ENSP00000381465.2
	MRO	ENST00000256425.6	TSL:1	c.100-147A>G		intron	N/A	ENSP00000256425.2
	MRO	ENST00000585524.5	TSL:1	n.245-147A>G		intron	N/A	ENSP00000465783.1

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

African (AFR) AF: 0.0789 AC: 1263 AN: 16006

American (AMR) AF: 0.111 AC: 2434 AN: 21956

Ashkenazi Jewish (ASJ) AF: 0.196 AC: 2984 AN: 15234

East Asian (EAS) AF: 0.0891 AC: 3009 AN: 33776

South Asian (SAS) AF: 0.219 AC: 11112 AN: 50782

European-Finnish (FIN) AF: 0.246 AC: 8342 AN: 33934

Middle Eastern (MID) AF: 0.165 AC: 445 AN: 2698

European-Non Finnish (NFE) AF: 0.287 AC: 117825 AN: 411012

Other (OTH) AF: 0.227 AC: 7211 AN: 31714

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

African (AFR) AF: 0.0808 AC: 3354 AN: 41504

American (AMR) AF: 0.136 AC: 2084 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.198 AC: 689 AN: 3472

East Asian (EAS) AF: 0.0876 AC: 453 AN: 5170

South Asian (SAS) AF: 0.217 AC: 1047 AN: 4820

European-Finnish (FIN) AF: 0.245 AC: 2584 AN: 10552

Middle Eastern (MID) AF: 0.143 AC: 42 AN: 294

European-Non Finnish (NFE) AF: 0.284 AC: 19282 AN: 67980

Other (OTH) AF: 0.180 AC: 380 AN: 2108

Alfa AF: 0.249 Hom.: 3339

Bravo AF: 0.180

Asia WGS AF: 0.178 AC: 619 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	2.1
DANN	Benign	0.76
PhyloP100		-0.18
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: rs2255672; hg19: chr18-48333367;