5-41033829-C-CTATCTATT

Variant names:

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

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP6_Moderate BA1

The NM_173489.5(MROH2B):​c.2241+8_2241+9insAATAGATA variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.19 in 1,318,344 control chromosomes in the GnomAD database, including 50,681 homozygotes. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.24 (5089 hom., cov: 0)
  • Exomes 𝑓: 0.18 (45592 hom.)
• Consequence: MROH2B NM_173489.5 splice_region, intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• 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 -10 ACMG points.

• BP6: Variant 5-41033829-C-CTATCTATT is Benign according to our data. Variant chr5-41033829-C-CTATCTATT is described in ClinVar as Benign. ClinVar VariationId is 403104.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.288 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MROH2B	NM_173489.5	c.2241+8_2241+9insAATAGATA		splice_region_variant, intron_variant	Intron 22 of 41	ENST00000399564.5	NP_775760.3
MROH2B	XM_011513952.2	c.2241+8_2241+9insAATAGATA		splice_region_variant, intron_variant	Intron 22 of 42		XP_011512254.1
MROH2B	XM_011513953.2	c.2055+8_2055+9insAATAGATA		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+9insAATAGATA		splice_region_variant, intron_variant	Intron 22 of 41	1	NM_173489.5	ENSP00000382476.4
MROH2B	ENST00000506092.6	c.906+8_906+9insAATAGATA		splice_region_variant, intron_variant	Intron 12 of 31	2		ENSP00000441504.1
MROH2B	ENST00000503890.5	n.1203+8_1203+9insAATAGATA		splice_region_variant, intron_variant	Intron 10 of 30	2
MROH2B	ENST00000515297.5	n.1629+8_1629+9insAATAGATA		splice_region_variant, intron_variant	Intron 16 of 35	5

Frequencies

GnomAD3 genomes AF: 0.244 AC: 35535 AN: 145896 Hom.: 5087 Cov.: 0

Gnomad AFR AF: 0.147

Gnomad AMI AF: 0.355

Gnomad AMR AF: 0.295

Gnomad ASJ AF: 0.276

Gnomad EAS AF: 0.148

Gnomad SAS AF: 0.236

Gnomad FIN AF: 0.276

Gnomad MID AF: 0.270

Gnomad NFE AF: 0.287

Gnomad OTH AF: 0.289

GnomAD2 exomes AF: 0.203 AC: 26860 AN: 132376 AF XY: 0.198

Gnomad AFR exome AF: 0.117

Gnomad AMR exome AF: 0.219

Gnomad ASJ exome AF: 0.218

Gnomad EAS exome AF: 0.118

Gnomad FIN exome AF: 0.249

Gnomad NFE exome AF: 0.224

Gnomad OTH exome AF: 0.207

GnomAD4 exome AF: 0.183 AC: 214323 AN: 1172334 Hom.: 45592 Cov.: 30 AF XY: 0.187 AC XY: 109235 AN XY: 583400

African (AFR) AF: 0.0988 AC: 2723 AN: 27570

American (AMR) AF: 0.233 AC: 7601 AN: 32572

Ashkenazi Jewish (ASJ) AF: 0.229 AC: 5064 AN: 22074

East Asian (EAS) AF: 0.123 AC: 4247 AN: 34652

South Asian (SAS) AF: 0.181 AC: 12725 AN: 70264

European-Finnish (FIN) AF: 0.263 AC: 12378 AN: 46982

Middle Eastern (MID) AF: 0.200 AC: 1022 AN: 5100

European-Non Finnish (NFE) AF: 0.180 AC: 159073 AN: 882956

Other (OTH) AF: 0.189 AC: 9490 AN: 50164

GnomAD4 genome AF: 0.243 AC: 35551 AN: 146010 Hom.: 5089 Cov.: 0 AF XY: 0.244 AC XY: 17348 AN XY: 71222

African (AFR) AF: 0.147 AC: 5714 AN: 38938

American (AMR) AF: 0.295 AC: 4319 AN: 14644

Ashkenazi Jewish (ASJ) AF: 0.276 AC: 920 AN: 3336

East Asian (EAS) AF: 0.148 AC: 744 AN: 5044

South Asian (SAS) AF: 0.236 AC: 1080 AN: 4572

European-Finnish (FIN) AF: 0.276 AC: 2777 AN: 10056

Middle Eastern (MID) AF: 0.252 AC: 71 AN: 282

European-Non Finnish (NFE) AF: 0.287 AC: 19041 AN: 66262

Other (OTH) AF: 0.287 AC: 575 AN: 2002

Alfa AF: 0.212 Hom.: 640

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Benign:1

Mar 29, 2016

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Variant identified in a genome or exome case(s) and assessed due to predicted null impact of the variant or pathogenic assertions in the literature or databases. Disclaimer: This variant has not undergone full assessment. The following are preliminary notes: Outside splice consensus. -

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;