Genetic Variant MROH2B:c.2241+8_2241+9insAATAA (chr5-41033829-C-CTTATT) – ACMG Classification: Benign (-8 pts)

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BS1BS2

The NM_173489.5(MROH2B):c.2241+8_2241+9insAATAA variant causes a splice region, 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
NM_173489.5 splice_region, intron

Scores

Not classified

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.238

Publications

3 publications found

Variant links:

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 links:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -8 ACMG points.

BS1

Variant frequency is greater than expected in population amr. GnomAdExome4 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 GnomAdExome4. There are 8060 alleles in the male GnomAdExome4 subpopulation. Median coverage is 30. This position passed quality control check.

BS2

High Homozygotes in GnomAdExome4 at 511 AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_173489.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MROH2B	NM_173489.5	MANE Select	c.2241+8_2241+9insAATAA		splice_region intron	N/A	NP_775760.3

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
MROH2B	ENST00000399564.5	TSL:1 MANE Select	c.2241+8_2241+9insAATAA	splice_region intron	N/A	ENSP00000382476.4	Q7Z745-1
MROH2B	ENST00000506092.6	TSL:2	c.906+8_906+9insAATAA	splice_region intron	N/A	ENSP00000441504.1	F5GZ06
MROH2B	ENST00000503890.5	TSL:2	n.1203+8_1203+9insAATAA	splice_region intron	N/A

Frequencies

GnomAD3 genomes

AF:

0.0184

AC:

2690

AN:

146052

Hom.:

Cov.:

show subpopulations

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

GnomAD2 exomes

AF:

0.0189

AC:

2497

AN:

132376

AF XY:

0.0187

show subpopulations

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 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.:

AF XY:

0.0137

AC XY:

8060

AN XY:

586674

show subpopulations

African (AFR)

AF:

0.00279

AC:

AN:

27640

American (AMR)

AF:

0.0369

AC:

1209

AN:

32764

Ashkenazi Jewish (ASJ)

AF:

0.00351

AC:

AN:

22206

East Asian (EAS)

AF:

0.0000287

AC:

AN:

34806

South Asian (SAS)

AF:

0.0188

AC:

1327

AN:

70722

European-Finnish (FIN)

AF:

0.0204

AC:

966

AN:

47352

Middle Eastern (MID)

AF:

0.00742

AC:

AN:

5122

European-Non Finnish (NFE)

AF:

0.0125

AC:

11082

AN:

887460

Other (OTH)

AF:

0.0136

AC:

685

AN:

50380

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.478

Heterozygous variant carriers

555

1110

1664

2219

2774

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

218

436

654

872

1090

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.0184

AC:

2690

AN:

146166

Hom.:

Cov.:

AF XY:

0.0179

AC XY:

1276

AN XY:

71298

show subpopulations

African (AFR)

AF:

0.00488

AC:

190

AN:

38950

American (AMR)

AF:

0.0311

AC:

456

AN:

14676

Ashkenazi Jewish (ASJ)

AF:

0.00659

AC:

AN:

3336

East Asian (EAS)

AF:

0.000198

AC:

AN:

5046

South Asian (SAS)

AF:

0.0179

AC:

AN:

4576

European-Finnish (FIN)

AF:

0.0209

AC:

211

AN:

10072

Middle Eastern (MID)

AF:

0.00709

AC:

AN:

282

European-Non Finnish (NFE)

AF:

0.0255

AC:

1695

AN:

66344

Other (OTH)

AF:

0.0154

AC:

AN:

2008

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

131

262

394

525

656

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

128

160

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0120

Hom.:

640

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

PhyloP100

-0.24

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

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

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over