5-41033829-C-CTTATT

Position:

• chr5-41033829-C-CTTATT

Variant summary

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

The ENST00000399564.5(MROH2B):​c.2241+8_2241+9insAATAA variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0131 in 1,178,452 control chromosomes in the GnomAD database, including 511 homozygotes. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.018 (47 hom., cov: 0)
  • Exomes 𝑓: 0.013 (511 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 = 0.0131 (15463/1178452) while in subpopulation AMR AF= 0.0369 (1209/32764). AF 95% confidence interval is 0.0352. There are 511 homozygotes in gnomad4_exome. There are 8060 alleles in male gnomad4_exome subpopulation. Median coverage is 30. This position pass quality control queck.
• BS2: High Homozygotes in GnomAdExome4 at 511 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MROH2B	NM_173489.5	c.2241+8_2241+9insAATAA		intron_variant		ENST00000399564.5	NP_775760.3
MROH2B	XM_011513952.2	c.2241+8_2241+9insAATAA		intron_variant			XP_011512254.1
MROH2B	XM_011513953.2	c.2055+8_2055+9insAATAA		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+9insAATAA		intron_variant		1	NM_173489.5	ENSP00000382476	P1
MROH2B	ENST00000506092.6	c.906+8_906+9insAATAA		intron_variant		2		ENSP00000441504
MROH2B	ENST00000503890.5	n.1203+8_1203+9insAATAA		intron_variant, non_coding_transcript_variant		2
MROH2B	ENST00000515297.5	n.1629+8_1629+9insAATAA		intron_variant, non_coding_transcript_variant		5

Frequencies

GnomAD3 genomes AF: 0.0184 AC: 2690 AN: 146052 Hom.: 47 Cov.: 0

Gnomad AFR AF: 0.00489

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0310

Gnomad ASJ AF: 0.00659

Gnomad EAS AF: 0.000198

Gnomad SAS AF: 0.0181

Gnomad FIN AF: 0.0209

Gnomad MID AF: 0.00987

Gnomad NFE AF: 0.0255

Gnomad OTH AF: 0.0161

GnomAD3 exomes AF: 0.0189 AC: 2497 AN: 132376 Hom.: 88 AF XY: 0.0187 AC XY: 1314 AN XY: 70404

Gnomad AFR exome AF: 0.00404

Gnomad AMR exome AF: 0.0358

Gnomad ASJ exome AF: 0.00310

Gnomad EAS exome AF: 0.0000987

Gnomad SAS exome AF: 0.0160

Gnomad FIN exome AF: 0.0183

Gnomad NFE exome AF: 0.0210

Gnomad OTH exome AF: 0.0197

GnomAD4 exome AF: 0.0131 AC: 15463 AN: 1178452 Hom.: 511 Cov.: 30 AF XY: 0.0137 AC XY: 8060 AN XY: 586674

Gnomad4 AFR exome AF: 0.00279

Gnomad4 AMR exome AF: 0.0369

Gnomad4 ASJ exome AF: 0.00351

Gnomad4 EAS exome AF: 0.0000287

Gnomad4 SAS exome AF: 0.0188

Gnomad4 FIN exome AF: 0.0204

Gnomad4 NFE exome AF: 0.0125

Gnomad4 OTH exome AF: 0.0136

GnomAD4 genome Data not reliable, filtered out with message: AS_VQSR AF: 0.0184 AC: 2690 AN: 146166 Hom.: 47 Cov.: 0 AF XY: 0.0179 AC XY: 1276 AN XY: 71298

Gnomad4 AFR AF: 0.00488

Gnomad4 AMR AF: 0.0311

Gnomad4 ASJ AF: 0.00659

Gnomad4 EAS AF: 0.000198

Gnomad4 SAS AF: 0.0179

Gnomad4 FIN AF: 0.0209

Gnomad4 NFE AF: 0.0255

Gnomad4 OTH AF: 0.0154

Alfa AF: 0.0120 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;