NM_173489.5:c.2241+8_2241+9insAATA

Variant names:

• chr5-41033829-C-CTATT
• rs70988830
• NM_173489.5:c.2241+8_2241+9insAATA

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
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.238
• Publications: 3 publications found

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

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.

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+9insAATA		splice_region intron	N/A	NP_775760.3

Ensembl Transcripts

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

Frequencies

GnomAD3 genomes AF: 0.232 AC: 33869 AN: 145860 Hom.: 4390 Cov.: 0

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

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.: 30 AF XY: 0.181 AC XY: 104356 AN XY: 576018

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

GnomAD4 genome Data not reliable, filtered out with message: AS_VQSR AF: 0.232 AC: 33874 AN: 145972 Hom.: 4389 Cov.: 0 AF XY: 0.230 AC XY: 16374 AN XY: 71182

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: 58 AN: 280

European-Non Finnish (NFE) AF: 0.252 AC: 16670 AN: 66264

Other (OTH) AF: 0.233 AC: 466 AN: 2002

Alfa AF: 0.226 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)

Splicing

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

Other links and lift over

dbSNP: rs70988830; hg19: chr5-41033931;