chr5-41019840-A-G

Position:

• chr5-41019840-A-G

Variant summary

Our verdict is Benign. Variant got -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

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=-0.97).
• 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/exons	MANE	Protein	UniProt
MROH2B	NM_173489.5	c.2442-822T>C		intron_variant		ENST00000399564.5	NP_775760.3
MROH2B	XM_011513952.2	c.2442-822T>C		intron_variant			XP_011512254.1
MROH2B	XM_011513953.2	c.2256-822T>C		intron_variant			XP_011512255.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MROH2B	ENST00000399564.5	c.2442-822T>C		intron_variant		1	NM_173489.5	ENSP00000382476	P1

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

Gnomad4 AFR AF: 0.883

Gnomad4 AMR AF: 0.906

Gnomad4 ASJ AF: 0.897

Gnomad4 EAS AF: 0.734

Gnomad4 SAS AF: 0.829

Gnomad4 FIN AF: 0.847

Gnomad4 NFE AF: 0.864

Gnomad4 OTH AF: 0.873

Alfa AF: 0.858 Hom.: 20177

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

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: rs10058056; hg19: chr5-41019942;