18-50813747-T-C

Variant names:

• chr18-50813747-T-C
• rs2218369
• NM_031939.6:c.-4-4343A>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.-4-4343A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.781 in 152,140 control chromosomes in the GnomAD database, including 46,876 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 0.78 (46876 hom., cov: 32)
• Consequence: MRO NM_031939.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.653
• Publications: 1 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=-0.95).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.836 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MRO	NM_031939.6	c.-4-4343A>G		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.-4-4343A>G		intron_variant	Intron 2 of 7	1	NM_031939.6	ENSP00000381465.2

Frequencies

GnomAD3 genomes AF: 0.781 AC: 118772 AN: 152022 Hom.: 46838 Cov.: 32

Gnomad AFR AF: 0.681

Gnomad AMI AF: 0.755

Gnomad AMR AF: 0.801

Gnomad ASJ AF: 0.781

Gnomad EAS AF: 0.585

Gnomad SAS AF: 0.858

Gnomad FIN AF: 0.826

Gnomad MID AF: 0.829

Gnomad NFE AF: 0.841

Gnomad OTH AF: 0.781

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

GnomAD4 genome AF: 0.781 AC: 118871 AN: 152140 Hom.: 46876 Cov.: 32 AF XY: 0.780 AC XY: 57983 AN XY: 74356

African (AFR) AF: 0.681 AC: 28253 AN: 41492

American (AMR) AF: 0.801 AC: 12235 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.781 AC: 2711 AN: 3470

East Asian (EAS) AF: 0.585 AC: 3020 AN: 5158

South Asian (SAS) AF: 0.858 AC: 4137 AN: 4820

European-Finnish (FIN) AF: 0.826 AC: 8748 AN: 10590

Middle Eastern (MID) AF: 0.820 AC: 241 AN: 294

European-Non Finnish (NFE) AF: 0.841 AC: 57185 AN: 68010

Other (OTH) AF: 0.783 AC: 1654 AN: 2112

Alfa AF: 0.812 Hom.: 6237

Bravo AF: 0.770

Asia WGS AF: 0.719 AC: 2501 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	2.7
DANN	Benign	0.82
PhyloP100		-0.65
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: rs2218369; hg19: chr18-48340117;