5-41019840-A-G

Variant names:

• chr5-41019840-A-G
• rs10058056
• NM_173489.5:c.2442-822T>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_173489.5(MROH2B):​c.2442-822T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.867 in 152,218 control chromosomes in the GnomAD database, including 57,402 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 0.87 (57402 hom., cov: 33)
• Consequence: MROH2B NM_173489.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.729
• 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]

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]

C7 Gene-Disease associations (from GenCC):

• complement component 7 deficiency

  Inheritance: AR Classification: STRONG Submitted by: Ambry Genetics, Illumina, Labcorp Genetics (formerly Invitae)

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.97).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.894 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MROH2B	NM_173489.5	c.2442-822T>C		intron_variant	Intron 24 of 41	ENST00000399564.5	NP_775760.3
MROH2B	XM_011513952.2	c.2442-822T>C		intron_variant	Intron 24 of 42		XP_011512254.1
MROH2B	XM_011513953.2	c.2256-822T>C		intron_variant	Intron 23 of 40		XP_011512255.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MROH2B	ENST00000399564.5	c.2442-822T>C		intron_variant	Intron 24 of 41	1	NM_173489.5	ENSP00000382476.4

Frequencies

GnomAD3 genomes AF: 0.867 AC: 131935 AN: 152100 Hom.: 57348 Cov.: 33

Gnomad AFR AF: 0.883

Gnomad AMI AF: 0.854

Gnomad AMR AF: 0.906

Gnomad ASJ AF: 0.897

Gnomad EAS AF: 0.734

Gnomad SAS AF: 0.828

Gnomad FIN AF: 0.847

Gnomad MID AF: 0.823

Gnomad NFE AF: 0.864

Gnomad OTH AF: 0.873

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

GnomAD4 genome AF: 0.867 AC: 132049 AN: 152218 Hom.: 57402 Cov.: 33 AF XY: 0.866 AC XY: 64463 AN XY: 74422

African (AFR) AF: 0.883 AC: 36661 AN: 41530

American (AMR) AF: 0.906 AC: 13862 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.897 AC: 3115 AN: 3472

East Asian (EAS) AF: 0.734 AC: 3800 AN: 5176

South Asian (SAS) AF: 0.829 AC: 4000 AN: 4824

European-Finnish (FIN) AF: 0.847 AC: 8974 AN: 10590

Middle Eastern (MID) AF: 0.820 AC: 241 AN: 294

European-Non Finnish (NFE) AF: 0.864 AC: 58772 AN: 68010

Other (OTH) AF: 0.873 AC: 1845 AN: 2114

Alfa AF: 0.860 Hom.: 23127

Bravo AF: 0.872

Asia WGS AF: 0.749 AC: 2605 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	0.44
DANN	Benign	0.49
PhyloP100		-0.73
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs10058056; hg19: chr5-41019942;