rs1450658

Variant names:

• chr5-41009140-C-T
• rs1450658
• NM_173489.5:c.3420+140G>A

Variant summary

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

The NM_173489.5(MROH2B):​c.3420+140G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.816 in 1,207,622 control chromosomes in the GnomAD database, including 403,735 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 0.82 (51845 hom., cov: 31)
  • Exomes 𝑓: 0.82 (351890 hom.)
• Consequence: MROH2B NM_173489.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.126

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=-0.9).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.857 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MROH2B	NM_173489.5	c.3420+140G>A		intron_variant	Intron 32 of 41	ENST00000399564.5	NP_775760.3
MROH2B	XM_011513952.2	c.3420+140G>A		intron_variant	Intron 32 of 42		XP_011512254.1
MROH2B	XM_011513953.2	c.3234+140G>A		intron_variant	Intron 31 of 40		XP_011512255.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MROH2B	ENST00000399564.5	c.3420+140G>A		intron_variant	Intron 32 of 41	1	NM_173489.5	ENSP00000382476.4

Frequencies

GnomAD3 genomes AF: 0.824 AC: 125183 AN: 151980 Hom.: 51804 Cov.: 31

Gnomad AFR AF: 0.865

Gnomad AMI AF: 0.687

Gnomad AMR AF: 0.861

Gnomad ASJ AF: 0.797

Gnomad EAS AF: 0.620

Gnomad SAS AF: 0.781

Gnomad FIN AF: 0.765

Gnomad MID AF: 0.756

Gnomad NFE AF: 0.821

Gnomad OTH AF: 0.825

GnomAD4 exome AF: 0.815 AC: 860325 AN: 1055524 Hom.: 351890 AF XY: 0.815 AC XY: 425317 AN XY: 521926

Gnomad4 AFR exome AF: 0.869

Gnomad4 AMR exome AF: 0.848

Gnomad4 ASJ exome AF: 0.786

Gnomad4 EAS exome AF: 0.632

Gnomad4 SAS exome AF: 0.796

Gnomad4 FIN exome AF: 0.773

Gnomad4 NFE exome AF: 0.825

Gnomad4 OTH exome AF: 0.805

GnomAD4 genome AF: 0.824 AC: 125281 AN: 152098 Hom.: 51845 Cov.: 31 AF XY: 0.821 AC XY: 61045 AN XY: 74338

Gnomad4 AFR AF: 0.865

Gnomad4 AMR AF: 0.861

Gnomad4 ASJ AF: 0.797

Gnomad4 EAS AF: 0.620

Gnomad4 SAS AF: 0.782

Gnomad4 FIN AF: 0.765

Gnomad4 NFE AF: 0.821

Gnomad4 OTH AF: 0.820

Alfa AF: 0.822 Hom.: 25961

Bravo AF: 0.830

Asia WGS AF: 0.664 AC: 2308 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	2.0
DANN	Benign	0.22

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: rs1450658; hg19: chr5-41009242; COSMIC: COSV68183691;