18-50809784-A-G

Variant names:

• chr18-50809784-A-G
• rs2586775
• NM_031939.6:c.-4-380T>C

Variant summary

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

The NM_031939.6(MRO):​c.-4-380T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.79 in 152,200 control chromosomes in the GnomAD database, including 47,833 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 0.79 (47833 hom., cov: 33)
• Consequence: MRO NM_031939.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.333
• Publications: 3 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=-1.01).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.841 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MRO	NM_031939.6	c.-4-380T>C		intron_variant	Intron 2 of 7	ENST00000398439.8	NP_114145.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MRO	ENST00000398439.8	c.-4-380T>C		intron_variant	Intron 2 of 7	1	NM_031939.6	ENSP00000381465.2

Frequencies

GnomAD3 genomes AF: 0.790 AC: 120160 AN: 152082 Hom.: 47800 Cov.: 33

Gnomad AFR AF: 0.694

Gnomad AMI AF: 0.753

Gnomad AMR AF: 0.802

Gnomad ASJ AF: 0.783

Gnomad EAS AF: 0.659

Gnomad SAS AF: 0.863

Gnomad FIN AF: 0.859

Gnomad MID AF: 0.829

Gnomad NFE AF: 0.840

Gnomad OTH AF: 0.795

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

GnomAD4 genome AF: 0.790 AC: 120254 AN: 152200 Hom.: 47833 Cov.: 33 AF XY: 0.790 AC XY: 58802 AN XY: 74402

African (AFR) AF: 0.694 AC: 28831 AN: 41516

American (AMR) AF: 0.802 AC: 12268 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.783 AC: 2720 AN: 3472

East Asian (EAS) AF: 0.659 AC: 3405 AN: 5164

South Asian (SAS) AF: 0.863 AC: 4169 AN: 4830

European-Finnish (FIN) AF: 0.859 AC: 9093 AN: 10586

Middle Eastern (MID) AF: 0.823 AC: 242 AN: 294

European-Non Finnish (NFE) AF: 0.840 AC: 57156 AN: 68020

Other (OTH) AF: 0.797 AC: 1683 AN: 2112

Alfa AF: 0.818 Hom.: 202574

Bravo AF: 0.777

Asia WGS AF: 0.759 AC: 2637 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	1.3
DANN	Benign	0.41
PhyloP100		-0.33
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: rs2586775; hg19: chr18-48336154;