5-41033829-C-CTATCTATCTATT

Position:

• chr5-41033829-C-CTATCTATCTATT

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BS1 BS2

The ENST00000399564.5(MROH2B):​c.2241+8_2241+9insAATAGATAGATA variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0259 in 1,177,910 control chromosomes in the GnomAD database, including 4,427 homozygotes. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.038 (181 hom., cov: 0)
  • Exomes 𝑓: 0.026 (4427 hom.)
  • Failed GnomAD Quality Control
• Consequence: MROH2B ENST00000399564.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.238

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]

ACMG classification

Verdict is Benign. Variant got -8 ACMG points.

• BS1: Variant frequency is greater than expected in population amr. gnomad4_exome allele frequency = 0.0259 (30544/1177910) while in subpopulation AMR AF= 0.0317 (1037/32750). AF 95% confidence interval is 0.0301. There are 4427 homozygotes in gnomad4_exome. There are 15468 alleles in male gnomad4_exome subpopulation. Median coverage is 30. This position pass quality control queck.
• BS2: High Homozygotes in GnomAdExome4 at 4427 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MROH2B	NM_173489.5	c.2241+8_2241+9insAATAGATAGATA		intron_variant		ENST00000399564.5	NP_775760.3
MROH2B	XM_011513952.2	c.2241+8_2241+9insAATAGATAGATA		intron_variant			XP_011512254.1
MROH2B	XM_011513953.2	c.2055+8_2055+9insAATAGATAGATA		intron_variant			XP_011512255.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MROH2B	ENST00000399564.5	c.2241+8_2241+9insAATAGATAGATA		intron_variant		1	NM_173489.5	ENSP00000382476	P1
MROH2B	ENST00000506092.6	c.906+8_906+9insAATAGATAGATA		intron_variant		2		ENSP00000441504
MROH2B	ENST00000503890.5	n.1203+8_1203+9insAATAGATAGATA		intron_variant, non_coding_transcript_variant		2
MROH2B	ENST00000515297.5	n.1629+8_1629+9insAATAGATAGATA		intron_variant, non_coding_transcript_variant		5

Frequencies

GnomAD3 genomes AF: 0.00 AC: 5565 AN: 146018 Hom.: 180 Cov.: 0 FAILED QC

Gnomad AFR AF: 0.0216

Gnomad AMI AF: 0.0434

Gnomad AMR AF: 0.0449

Gnomad ASJ AF: 0.0486

Gnomad EAS AF: 0.0243

Gnomad SAS AF: 0.0319

Gnomad FIN AF: 0.0528

Gnomad MID AF: 0.0329

Gnomad NFE AF: 0.0450

Gnomad OTH AF: 0.0372

GnomAD3 exomes AF: 0.0294 AC: 3886 AN: 132376 Hom.: 484 AF XY: 0.0280 AC XY: 1970 AN XY: 70404

Gnomad AFR exome AF: 0.0160

Gnomad AMR exome AF: 0.0270

Gnomad ASJ exome AF: 0.0334

Gnomad EAS exome AF: 0.0134

Gnomad SAS exome AF: 0.0209

Gnomad FIN exome AF: 0.0476

Gnomad NFE exome AF: 0.0327

Gnomad OTH exome AF: 0.0291

GnomAD4 exome AF: 0.0259 AC: 30544 AN: 1177910 Hom.: 4427 Cov.: 30 AF XY: 0.0264 AC XY: 15468 AN XY: 586402

Gnomad4 AFR exome AF: 0.0144

Gnomad4 AMR exome AF: 0.0317

Gnomad4 ASJ exome AF: 0.0389

Gnomad4 EAS exome AF: 0.0141

Gnomad4 SAS exome AF: 0.0237

Gnomad4 FIN exome AF: 0.0487

Gnomad4 NFE exome AF: 0.0251

Gnomad4 OTH exome AF: 0.0280

GnomAD4 genome Data not reliable, filtered out with message: AS_VQSR AF: 0.0381 AC: 5573 AN: 146132 Hom.: 181 Cov.: 0 AF XY: 0.0385 AC XY: 2746 AN XY: 71282

Gnomad4 AFR AF: 0.0216

Gnomad4 AMR AF: 0.0450

Gnomad4 ASJ AF: 0.0486

Gnomad4 EAS AF: 0.0248

Gnomad4 SAS AF: 0.0317

Gnomad4 FIN AF: 0.0528

Gnomad4 NFE AF: 0.0450

Gnomad4 OTH AF: 0.0388

Alfa AF: 0.0327 Hom.: 640

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs70988830; hg19: chr5-41033931;