5-41004294-G-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_173489.5(MROH2B):c.4194+52C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.869 in 1,578,454 control chromosomes in the GnomAD database, including 596,487 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.85 (55324 hom., cov: 31)
  • Exomes 𝑓: 0.87 (541163 hom.)
• Consequence: MROH2B NM_173489.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.315

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]

C7 (HGNC:1346): (complement C7) This gene encodes a serum glycoprotein that forms a membrane attack complex together with complement components C5b, C6, C8, and C9 as part of the terminal complement pathway of the innate immune system. The protein encoded by this gene contains a cholesterol-dependent cytolysin/membrane attack complex/perforin-like (CDC/MACPF) domain and belongs to a large family of structurally related molecules that form pores involved in host immunity and bacterial pathogenesis. This protein initiates membrane attack complex formation by binding the C5b-C6 subcomplex and inserts into the phospholipid bilayer, serving as a membrane anchor. Mutations in this gene are associated with a rare disorder called C7 deficiency. [provided by RefSeq, Nov 2016]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.866 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MROH2B	NM_173489.5	c.4194+52C>A		intron_variant		ENST00000399564.5
MROH2B	XM_011513952.2	c.4194+52C>A		intron_variant
MROH2B	XM_011513953.2	c.4008+52C>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MROH2B	ENST00000399564.5	c.4194+52C>A		intron_variant		1	NM_173489.5	P1

Frequencies

GnomAD3 genomes AF: 0.852 AC: 129456 AN: 151996 Hom.: 55280 Cov.: 31

Gnomad AFR AF: 0.803

Gnomad AMI AF: 0.818

Gnomad AMR AF: 0.843

Gnomad ASJ AF: 0.883

Gnomad EAS AF: 0.864

Gnomad SAS AF: 0.885

Gnomad FIN AF: 0.896

Gnomad MID AF: 0.845

Gnomad NFE AF: 0.872

Gnomad OTH AF: 0.851

GnomAD4 exome AF: 0.871 AC: 1242056 AN: 1426340 Hom.: 541163 AF XY: 0.872 AC XY: 616989 AN XY: 707952

Gnomad4 AFR exome AF: 0.802

Gnomad4 AMR exome AF: 0.858

Gnomad4 ASJ exome AF: 0.882

Gnomad4 EAS exome AF: 0.885

Gnomad4 SAS exome AF: 0.884

Gnomad4 FIN exome AF: 0.895

Gnomad4 NFE exome AF: 0.871

Gnomad4 OTH exome AF: 0.864

GnomAD4 genome AF: 0.852 AC: 129557 AN: 152114 Hom.: 55324 Cov.: 31 AF XY: 0.853 AC XY: 63416 AN XY: 74366

Gnomad4 AFR AF: 0.803

Gnomad4 AMR AF: 0.843

Gnomad4 ASJ AF: 0.883

Gnomad4 EAS AF: 0.865

Gnomad4 SAS AF: 0.885

Gnomad4 FIN AF: 0.896

Gnomad4 NFE AF: 0.872

Gnomad4 OTH AF: 0.851

Alfa AF: 0.860 Hom.: 13313

Bravo AF: 0.847

Asia WGS AF: 0.890 AC: 3092 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
Cadd	Benign	3.3
Dann	Benign	0.67

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

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

Publications

LitVar

Other links and lift over

dbSNP: rs7712140; hg19: chr5-41004396;