5-41000241-G-A

Position:

• chr5-41000241-G-A

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BA1

The NM_173489.5(MROH2B):​c.4461C>T​(p.Tyr1487Tyr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.681 in 1,613,428 control chromosomes in the GnomAD database, including 375,532 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 0.67 (33838 hom., cov: 31)
  • Exomes 𝑓: 0.68 (341694 hom.)
• Consequence: MROH2B NM_173489.5 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.66

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 -8 ACMG points.

• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.692 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MROH2B	NM_173489.5	c.4461C>T	p.Tyr1487Tyr	synonymous_variant	39/42	ENST00000399564.5	NP_775760.3
MROH2B	XM_011513952.2	c.4461C>T	p.Tyr1487Tyr	synonymous_variant	39/43		XP_011512254.1
MROH2B	XM_011513953.2	c.4275C>T	p.Tyr1425Tyr	synonymous_variant	38/41		XP_011512255.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MROH2B	ENST00000399564.5	c.4461C>T	p.Tyr1487Tyr	synonymous_variant	39/42	1	NM_173489.5	ENSP00000382476.4

Frequencies

GnomAD3 genomes AF: 0.665 AC: 101016 AN: 151886 Hom.: 33818 Cov.: 31

Gnomad AFR AF: 0.620

Gnomad AMI AF: 0.658

Gnomad AMR AF: 0.627

Gnomad ASJ AF: 0.655

Gnomad EAS AF: 0.675

Gnomad SAS AF: 0.559

Gnomad FIN AF: 0.736

Gnomad MID AF: 0.665

Gnomad NFE AF: 0.697

Gnomad OTH AF: 0.668

GnomAD3 exomes AF: 0.660 AC: 164170 AN: 248640 Hom.: 54731 AF XY: 0.656 AC XY: 88457 AN XY: 134854

Gnomad AFR exome AF: 0.619

Gnomad AMR exome AF: 0.610

Gnomad ASJ exome AF: 0.660

Gnomad EAS exome AF: 0.683

Gnomad SAS exome AF: 0.547

Gnomad FIN exome AF: 0.734

Gnomad NFE exome AF: 0.694

Gnomad OTH exome AF: 0.664

GnomAD4 exome AF: 0.682 AC: 996895 AN: 1461424 Hom.: 341694 Cov.: 56 AF XY: 0.678 AC XY: 493194 AN XY: 726988

Gnomad4 AFR exome AF: 0.623

Gnomad4 AMR exome AF: 0.613

Gnomad4 ASJ exome AF: 0.662

Gnomad4 EAS exome AF: 0.681

Gnomad4 SAS exome AF: 0.544

Gnomad4 FIN exome AF: 0.739

Gnomad4 NFE exome AF: 0.696

Gnomad4 OTH exome AF: 0.671

GnomAD4 genome AF: 0.665 AC: 101089 AN: 152004 Hom.: 33838 Cov.: 31 AF XY: 0.663 AC XY: 49308 AN XY: 74320

Gnomad4 AFR AF: 0.620

Gnomad4 AMR AF: 0.627

Gnomad4 ASJ AF: 0.655

Gnomad4 EAS AF: 0.676

Gnomad4 SAS AF: 0.558

Gnomad4 FIN AF: 0.736

Gnomad4 NFE AF: 0.697

Gnomad4 OTH AF: 0.668

Alfa AF: 0.681 Hom.: 57887

Bravo AF: 0.657

Asia WGS AF: 0.620 AC: 2157 AN: 3478

EpiCase AF: 0.687

EpiControl AF: 0.683

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.027
DANN	Benign	0.26

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.25		Details are displayed if max score is > 0.2
DS_DL_spliceai		0.25		Position offset: -21

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs1001420; hg19: chr5-41000343; COSMIC: COSV68181090; COSMIC: COSV68181090;