Genetic Variant NM_173489.5:c.2241+8_2241+9insAATAAGATAGATA (chr5-41033829-C-CTATCTATCTTATT) – ACMG Classification: Likely_benign (-4 pts)

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BS2

The NM_173489.5(MROH2B):c.2241+8_2241+9insAATAAGATAGATA variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000137 in 1,324,998 control chromosomes in the GnomAD database, including 4 homozygotes. It is difficult to determine the true allele frequency of this variant because it is of type INS_BIG, and the frequency of such variant types in population databases may be underestimated and unreliable. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.00021 ( 0 hom., cov: 0)

Exomes 𝑓: 0.00013 ( 4 hom. )

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: Likely_benign. The variant received -4 ACMG points.

BS2

High Homozygotes in GnomAdExome4 at 4 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+9insAATAAGATAGATA		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+9insAATAAGATAGATA	splice_region intron	N/A	ENSP00000382476.4	Q7Z745-1
MROH2B	ENST00000506092.6	TSL:2	c.906+8_906+9insAATAAGATAGATA	splice_region intron	N/A	ENSP00000441504.1	F5GZ06
MROH2B	ENST00000503890.5	TSL:2	n.1203+8_1203+9insAATAAGATAGATA	splice_region intron	N/A

Frequencies

GnomAD3 genomes

AF:

0.000212

AC:

AN:

146062

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000258

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000750

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000437

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000256

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.000128

AC:

151

AN:

1178822

Hom.:

Cov.:

AF XY:

0.000153

AC XY:

AN XY:

586882

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

27640

American (AMR)

AF:

0.000488

AC:

AN:

32794

Ashkenazi Jewish (ASJ)

AF:

0.0000901

AC:

AN:

22206

East Asian (EAS)

AF:

0.00

AC:

AN:

34806

South Asian (SAS)

AF:

0.000339

AC:

AN:

70750

European-Finnish (FIN)

AF:

0.0000633

AC:

AN:

47382

Middle Eastern (MID)

AF:

0.000195

AC:

AN:

5122

European-Non Finnish (NFE)

AF:

0.000115

AC:

102

AN:

887726

Other (OTH)

AF:

0.0000595

AC:

AN:

50396

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.463

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

<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

AF:

0.000212

AC:

AN:

146176

Hom.:

Cov.:

AF XY:

0.000224

AC XY:

AN XY:

71304

show subpopulations

African (AFR)

AF:

0.0000257

AC:

AN:

38950

American (AMR)

AF:

0.000749

AC:

AN:

14678

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3336

East Asian (EAS)

AF:

0.00

AC:

AN:

5046

South Asian (SAS)

AF:

0.000437

AC:

AN:

4576

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10074

Middle Eastern (MID)

AF:

0.00

AC:

AN:

282

European-Non Finnish (NFE)

AF:

0.000256

AC:

AN:

66350

Other (OTH)

AF:

0.00

AC:

AN:

2008

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.507

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<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:

0.00

Hom.:

640

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

PhyloP100

-0.24

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