rs896117

Positions:

• chr5-40999317-G-A

Variant summary

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

The NM_173489.5(MROH2B):​c.4585+360C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.268 in 152,024 control chromosomes in the GnomAD database, including 5,658 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 0.27 (5658 hom., cov: 32)
• Consequence: MROH2B NM_173489.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.00300

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=-0.87).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.362 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MROH2B	NM_173489.5	c.4585+360C>T		intron_variant		ENST00000399564.5	NP_775760.3
MROH2B	XM_011513952.2	c.4585+360C>T		intron_variant			XP_011512254.1
MROH2B	XM_011513953.2	c.4399+360C>T		intron_variant			XP_011512255.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MROH2B	ENST00000399564.5	c.4585+360C>T		intron_variant		1	NM_173489.5	ENSP00000382476.4

Frequencies

GnomAD3 genomes AF: 0.268 AC: 40741 AN: 151906 Hom.: 5647 Cov.: 32

Gnomad AFR AF: 0.315

Gnomad AMI AF: 0.175

Gnomad AMR AF: 0.274

Gnomad ASJ AF: 0.285

Gnomad EAS AF: 0.178

Gnomad SAS AF: 0.376

Gnomad FIN AF: 0.216

Gnomad MID AF: 0.266

Gnomad NFE AF: 0.246

Gnomad OTH AF: 0.253

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.268 AC: 40783 AN: 152024 Hom.: 5658 Cov.: 32 AF XY: 0.269 AC XY: 19953 AN XY: 74296

Gnomad4 AFR AF: 0.315

Gnomad4 AMR AF: 0.274

Gnomad4 ASJ AF: 0.285

Gnomad4 EAS AF: 0.178

Gnomad4 SAS AF: 0.377

Gnomad4 FIN AF: 0.216

Gnomad4 NFE AF: 0.246

Gnomad4 OTH AF: 0.252

Alfa AF: 0.257 Hom.: 6538

Bravo AF: 0.273

Asia WGS AF: 0.286 AC: 995 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	2.4
DANN	Benign	0.49

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: rs896117; hg19: chr5-40999419;