5-41033829-C-CTATCTATCTATT

Variant names:

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

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BS1 BS2

The NM_173489.5(MROH2B):​c.2241+8_2241+9insAATAGATAGATA variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0259 in 1,177,910 control chromosomes in the GnomAD database, including 4,427 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 0.038 (181 hom., cov: 0)
  • Exomes 𝑓: 0.026 (4427 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.

• BS1: Variant frequency is greater than expected in population amr. GnomAdExome4 allele frequency = 0.0259 (30544/1177910) while in subpopulation AMR AF = 0.0317 (1037/32750). AF 95% confidence interval is 0.0301. There are 4427 homozygotes in GnomAdExome4. There are 15468 alleles in the male GnomAdExome4 subpopulation. Median coverage is 30. This position passed quality control check.
• BS2: High Homozygotes in GnomAdExome4 at 4427 AR gene

Transcripts

RefSeq

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

Ensembl

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

Frequencies

GnomAD3 genomes AF: 0.0381 AC: 5565 AN: 146018 Hom.: 180 Cov.: 0

Gnomad AFR AF: 0.0216

Gnomad AMI AF: 0.0434

Gnomad AMR AF: 0.0449

Gnomad ASJ AF: 0.0486

Gnomad EAS AF: 0.0243

Gnomad SAS AF: 0.0319

Gnomad FIN AF: 0.0528

Gnomad MID AF: 0.0329

Gnomad NFE AF: 0.0450

Gnomad OTH AF: 0.0372

GnomAD2 exomes AF: 0.0294 AC: 3886 AN: 132376 AF XY: 0.0280

Gnomad AFR exome AF: 0.0160

Gnomad AMR exome AF: 0.0270

Gnomad ASJ exome AF: 0.0334

Gnomad EAS exome AF: 0.0134

Gnomad FIN exome AF: 0.0476

Gnomad NFE exome AF: 0.0327

Gnomad OTH exome AF: 0.0291

GnomAD4 exome AF: 0.0259 AC: 30544 AN: 1177910 Hom.: 4427 Cov.: 30 AF XY: 0.0264 AC XY: 15468 AN XY: 586402

African (AFR) AF: 0.0144 AC: 399 AN: 27628

American (AMR) AF: 0.0317 AC: 1037 AN: 32750

Ashkenazi Jewish (ASJ) AF: 0.0389 AC: 863 AN: 22182

East Asian (EAS) AF: 0.0141 AC: 490 AN: 34796

South Asian (SAS) AF: 0.0237 AC: 1673 AN: 70680

European-Finnish (FIN) AF: 0.0487 AC: 2304 AN: 47296

Middle Eastern (MID) AF: 0.0248 AC: 127 AN: 5114

European-Non Finnish (NFE) AF: 0.0251 AC: 22240 AN: 887118

Other (OTH) AF: 0.0280 AC: 1411 AN: 50346

GnomAD4 genome Data not reliable, filtered out with message: AS_VQSR AF: 0.0381 AC: 5573 AN: 146132 Hom.: 181 Cov.: 0 AF XY: 0.0385 AC XY: 2746 AN XY: 71282

African (AFR) AF: 0.0216 AC: 840 AN: 38942

American (AMR) AF: 0.0450 AC: 660 AN: 14672

Ashkenazi Jewish (ASJ) AF: 0.0486 AC: 162 AN: 3336

East Asian (EAS) AF: 0.0248 AC: 125 AN: 5046

South Asian (SAS) AF: 0.0317 AC: 145 AN: 4576

European-Finnish (FIN) AF: 0.0528 AC: 531 AN: 10064

Middle Eastern (MID) AF: 0.0355 AC: 10 AN: 282

European-Non Finnish (NFE) AF: 0.0450 AC: 2984 AN: 66330

Other (OTH) AF: 0.0388 AC: 78 AN: 2008

Alfa AF: 0.0327 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)

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;