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

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BA1

The NM_173489.5(MROH2B):c.2241+8_2241+9insAATA variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.177 in 1,157,850 control chromosomes in the GnomAD database, including 41,970 homozygotes. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.23 ( 4389 hom., cov: 0)

Exomes 𝑓: 0.18 ( 41970 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.

BA1

GnomAdExome4 highest subpopulation (MID) allele frequency at 95% confidence interval = 0.198 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein
MROH2B	NM_173489.5 link	c.2241+8_2241+9insAATA	splice_region_variant, intron_variant	Intron 22 of 41	ENST00000399564.5	NP_775760.3
MROH2B	XM_011513952.2 link	c.2241+8_2241+9insAATA	splice_region_variant, intron_variant	Intron 22 of 42		XP_011512254.1
MROH2B	XM_011513953.2 link	c.2055+8_2055+9insAATA	splice_region_variant, intron_variant	Intron 21 of 40		XP_011512255.1

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein	UniProt
MROH2B	ENST00000399564.5 link	c.2241+8_2241+9insAATA	splice_region_variant, intron_variant	Intron 22 of 41	1	NM_173489.5	ENSP00000382476.4	Q7Z745-1
MROH2B	ENST00000506092.6 link	c.906+8_906+9insAATA	splice_region_variant, intron_variant	Intron 12 of 31	2		ENSP00000441504.1	F5GZ06
MROH2B	ENST00000503890.5 link	n.1203+8_1203+9insAATA	splice_region_variant, intron_variant	Intron 10 of 30	2
MROH2B	ENST00000515297.5 link	n.1629+8_1629+9insAATA	splice_region_variant, intron_variant	Intron 16 of 35	5

Frequencies

GnomAD3 genomes

AF:

0.232

AC:

33869

AN:

145860

Hom.:

4390

Cov.:

show subpopulations

Gnomad AFR

AF:

0.205

Gnomad AMI

AF:

0.251

Gnomad AMR

AF:

0.220

Gnomad ASJ

AF:

0.334

Gnomad EAS

AF:

0.150

Gnomad SAS

AF:

0.242

Gnomad FIN

AF:

0.231

Gnomad MID

AF:

0.205

Gnomad NFE

AF:

0.252

Gnomad OTH

AF:

0.232

GnomAD2 exomes

AF:

0.222

AC:

29395

AN:

132376

AF XY:

0.222

show subpopulations

Gnomad AFR exome

AF:

0.185

Gnomad AMR exome

AF:

0.208

Gnomad ASJ exome

AF:

0.302

Gnomad EAS exome

AF:

0.139

Gnomad FIN exome

AF:

0.227

Gnomad NFE exome

AF:

0.241

Gnomad OTH exome

AF:

0.237

GnomAD4 exome

AF:

0.177

AC:

205099

AN:

1157850

Hom.:

41970

Cov.:

AF XY:

0.181

AC XY:

104356

AN XY:

576018

show subpopulations

African (AFR)

AF:

0.143

AC:

3916

AN:

27362

American (AMR)

AF:

0.202

AC:

6490

AN:

32074

Ashkenazi Jewish (ASJ)

AF:

0.274

AC:

5960

AN:

21730

East Asian (EAS)

AF:

0.120

AC:

4140

AN:

34388

South Asian (SAS)

AF:

0.198

AC:

13742

AN:

69544

European-Finnish (FIN)

AF:

0.225

AC:

10332

AN:

45992

Middle Eastern (MID)

AF:

0.208

AC:

1050

AN:

5038

European-Non Finnish (NFE)

AF:

0.172

AC:

150384

AN:

872284

Other (OTH)

AF:

0.184

AC:

9085

AN:

49438

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.484

Heterozygous variant carriers

4474

8948

13421

17895

22369

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

3164

6328

9492

12656

15820

<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:

0.232

AC:

33874

AN:

145972

Hom.:

4389

Cov.:

AF XY:

0.230

AC XY:

16374

AN XY:

71182

show subpopulations

African (AFR)

AF:

0.204

AC:

7953

AN:

38920

American (AMR)

AF:

0.219

AC:

3213

AN:

14652

Ashkenazi Jewish (ASJ)

AF:

0.334

AC:

1114

AN:

3332

East Asian (EAS)

AF:

0.150

AC:

757

AN:

5046

South Asian (SAS)

AF:

0.242

AC:

1104

AN:

4570

European-Finnish (FIN)

AF:

0.231

AC:

2320

AN:

10032

Middle Eastern (MID)

AF:

0.207

AC:

AN:

280

European-Non Finnish (NFE)

AF:

0.252

AC:

16670

AN:

66264

Other (OTH)

AF:

0.233

AC:

466

AN:

2002

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.498

Heterozygous variant carriers

1189

2377

3566

4754

5943

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

364

728

1092

1456

1820

<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:

0.226

Hom.:

640

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

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

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over