rs1530812

chr5-41000050-G-Achr5-41000050-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.4482+170C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.506 in 861,718 control chromosomes in the GnomAD database, including 110,972 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 0.48 (17644 hom., cov: 33)
  • Exomes 𝑓: 0.51 (93328 hom.)
• Consequence: MROH2B NM_173489.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.83

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=-0.85).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.606 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MROH2B	NM_173489.5	c.4482+170C>T		intron_variant		ENST00000399564.5
MROH2B	XM_011513952.2	c.4482+170C>T		intron_variant
MROH2B	XM_011513953.2	c.4296+170C>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MROH2B	ENST00000399564.5	c.4482+170C>T		intron_variant		1	NM_173489.5	P1

Frequencies

GnomAD3 genomes AF: 0.478 AC: 72641 AN: 151998 Hom.: 17628 Cov.: 33

Gnomad AFR AF: 0.420

Gnomad AMI AF: 0.381

Gnomad AMR AF: 0.459

Gnomad ASJ AF: 0.562

Gnomad EAS AF: 0.587

Gnomad SAS AF: 0.625

Gnomad FIN AF: 0.473

Gnomad MID AF: 0.576

Gnomad NFE AF: 0.496

Gnomad OTH AF: 0.464

GnomAD4 exome AF: 0.511 AC: 362936 AN: 709600 Hom.: 93328 Cov.: 9 AF XY: 0.516 AC XY: 186526 AN XY: 361718

Gnomad4 AFR exome AF: 0.420

Gnomad4 AMR exome AF: 0.468

Gnomad4 ASJ exome AF: 0.555

Gnomad4 EAS exome AF: 0.582

Gnomad4 SAS exome AF: 0.618

Gnomad4 FIN exome AF: 0.472

Gnomad4 NFE exome AF: 0.503

Gnomad4 OTH exome AF: 0.517

GnomAD4 genome AF: 0.478 AC: 72702 AN: 152118 Hom.: 17644 Cov.: 33 AF XY: 0.480 AC XY: 35665 AN XY: 74358

Gnomad4 AFR AF: 0.420

Gnomad4 AMR AF: 0.459

Gnomad4 ASJ AF: 0.562

Gnomad4 EAS AF: 0.586

Gnomad4 SAS AF: 0.625

Gnomad4 FIN AF: 0.473

Gnomad4 NFE AF: 0.496

Gnomad4 OTH AF: 0.468

Alfa AF: 0.497 Hom.: 8615

Bravo AF: 0.475

Asia WGS AF: 0.623 AC: 2165 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
Cadd	Benign	8.4
Dann	Benign	0.20

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs1530812; hg19: chr5-41000152; COSMIC: COSV68182126;