5-41000090-A-T

Position:

• chr5-41000090-A-T

Variant summary

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

The NM_173489.5(MROH2B):​c.4482+130T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.438 in 1,224,304 control chromosomes in the GnomAD database, including 119,350 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 0.46 (16089 hom., cov: 32)
  • Exomes 𝑓: 0.44 (103261 hom.)
• Consequence: MROH2B NM_173489.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.164

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=-0.83).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.51 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MROH2B	NM_173489.5	c.4482+130T>A		intron_variant		ENST00000399564.5	NP_775760.3
MROH2B	XM_011513952.2	c.4482+130T>A		intron_variant			XP_011512254.1
MROH2B	XM_011513953.2	c.4296+130T>A		intron_variant			XP_011512255.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MROH2B	ENST00000399564.5	c.4482+130T>A		intron_variant		1	NM_173489.5	ENSP00000382476.4

Frequencies

GnomAD3 genomes AF: 0.456 AC: 69265 AN: 151930 Hom.: 16079 Cov.: 32

Gnomad AFR AF: 0.516

Gnomad AMI AF: 0.456

Gnomad AMR AF: 0.441

Gnomad ASJ AF: 0.377

Gnomad EAS AF: 0.280

Gnomad SAS AF: 0.312

Gnomad FIN AF: 0.480

Gnomad MID AF: 0.358

Gnomad NFE AF: 0.447

Gnomad OTH AF: 0.457

GnomAD4 exome AF: 0.436 AC: 467338 AN: 1072256 Hom.: 103261 Cov.: 14 AF XY: 0.432 AC XY: 232964 AN XY: 539376

Gnomad4 AFR exome AF: 0.524

Gnomad4 AMR exome AF: 0.428

Gnomad4 ASJ exome AF: 0.382

Gnomad4 EAS exome AF: 0.303

Gnomad4 SAS exome AF: 0.317

Gnomad4 FIN exome AF: 0.485

Gnomad4 NFE exome AF: 0.448

Gnomad4 OTH exome AF: 0.422

GnomAD4 genome AF: 0.456 AC: 69320 AN: 152048 Hom.: 16089 Cov.: 32 AF XY: 0.453 AC XY: 33666 AN XY: 74318

Gnomad4 AFR AF: 0.516

Gnomad4 AMR AF: 0.441

Gnomad4 ASJ AF: 0.377

Gnomad4 EAS AF: 0.281

Gnomad4 SAS AF: 0.312

Gnomad4 FIN AF: 0.480

Gnomad4 NFE AF: 0.447

Gnomad4 OTH AF: 0.452

Alfa AF: 0.463 Hom.: 2035

Bravo AF: 0.455

Asia WGS AF: 0.286 AC: 996 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	3.1
DANN	Benign	0.59

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: rs3817324; hg19: chr5-41000192; COSMIC: COSV68181083; COSMIC: COSV68181083;