5-41004294-G-T

Position:

• chr5-41004294-G-T

Variant summary

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

The NM_173489.5(MROH2B):​c.4194+52C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.869 in 1,578,454 control chromosomes in the GnomAD database, including 596,487 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 0.85 (55324 hom., cov: 31)
  • Exomes 𝑓: 0.87 (541163 hom.)
• Consequence: MROH2B NM_173489.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.315

Genes affected

MROH2B (HGNC:26857): (maestro heat like repeat family member 2B) Predicted to be involved in protein kinase A signaling. Predicted to be located in acrosomal vesicle and sperm midpiece. [provided by Alliance of Genome Resources, Apr 2022]

MROH2B (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.866 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MROH2B	NM_173489.5	c.4194+52C>A		intron_variant		ENST00000399564.5	NP_775760.3
MROH2B	XM_011513952.2	c.4194+52C>A		intron_variant			XP_011512254.1
MROH2B	XM_011513953.2	c.4008+52C>A		intron_variant			XP_011512255.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MROH2B	ENST00000399564.5	c.4194+52C>A		intron_variant		1	NM_173489.5	ENSP00000382476.4

Frequencies

GnomAD3 genomes AF: 0.852 AC: 129456 AN: 151996 Hom.: 55280 Cov.: 31

Gnomad AFR AF: 0.803

Gnomad AMI AF: 0.818

Gnomad AMR AF: 0.843

Gnomad ASJ AF: 0.883

Gnomad EAS AF: 0.864

Gnomad SAS AF: 0.885

Gnomad FIN AF: 0.896

Gnomad MID AF: 0.845

Gnomad NFE AF: 0.872

Gnomad OTH AF: 0.851

GnomAD4 exome AF: 0.871 AC: 1242056 AN: 1426340 Hom.: 541163 AF XY: 0.872 AC XY: 616989 AN XY: 707952

Gnomad4 AFR exome AF: 0.802

Gnomad4 AMR exome AF: 0.858

Gnomad4 ASJ exome AF: 0.882

Gnomad4 EAS exome AF: 0.885

Gnomad4 SAS exome AF: 0.884

Gnomad4 FIN exome AF: 0.895

Gnomad4 NFE exome AF: 0.871

Gnomad4 OTH exome AF: 0.864

GnomAD4 genome AF: 0.852 AC: 129557 AN: 152114 Hom.: 55324 Cov.: 31 AF XY: 0.853 AC XY: 63416 AN XY: 74366

Gnomad4 AFR AF: 0.803

Gnomad4 AMR AF: 0.843

Gnomad4 ASJ AF: 0.883

Gnomad4 EAS AF: 0.865

Gnomad4 SAS AF: 0.885

Gnomad4 FIN AF: 0.896

Gnomad4 NFE AF: 0.872

Gnomad4 OTH AF: 0.851

Alfa AF: 0.860 Hom.: 13313

Bravo AF: 0.847

Asia WGS AF: 0.890 AC: 3092 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	3.3
DANN	Benign	0.67

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: rs7712140; hg19: chr5-41004396;