5-41004294-G-T

Variant names:

• chr5-41004294-G-T
• rs7712140
• NM_173489.5:c.4194+52C>A

Variant summary

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

The NM_173489.5(MROH2B):​c.4194+52C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.869 in 1,578,454 control chromosomes in the GnomAD database, including 596,487 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 0.85 (55324 hom., cov: 31)
  • Exomes 𝑓: 0.87 (541163 hom.)
• Consequence: MROH2B NM_173489.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.315
• Publications: 5 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=-0.88).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.866 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MROH2B	NM_173489.5	c.4194+52C>A		intron_variant	Intron 37 of 41	ENST00000399564.5	NP_775760.3
MROH2B	XM_011513952.2	c.4194+52C>A		intron_variant	Intron 37 of 42		XP_011512254.1
MROH2B	XM_011513953.2	c.4008+52C>A		intron_variant	Intron 36 of 40		XP_011512255.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MROH2B	ENST00000399564.5	c.4194+52C>A		intron_variant	Intron 37 of 41	1	NM_173489.5	ENSP00000382476.4

Frequencies

GnomAD3 genomes AF: 0.852 AC: 129456 AN: 151996 Hom.: 55280 Cov.: 31

Gnomad AFR AF: 0.803

Gnomad AMI AF: 0.818

Gnomad AMR AF: 0.843

Gnomad ASJ AF: 0.883

Gnomad EAS AF: 0.864

Gnomad SAS AF: 0.885

Gnomad FIN AF: 0.896

Gnomad MID AF: 0.845

Gnomad NFE AF: 0.872

Gnomad OTH AF: 0.851

GnomAD4 exome AF: 0.871 AC: 1242056 AN: 1426340 Hom.: 541163 AF XY: 0.872 AC XY: 616989 AN XY: 707952

African (AFR) AF: 0.802 AC: 25747 AN: 32088

American (AMR) AF: 0.858 AC: 34417 AN: 40102

Ashkenazi Jewish (ASJ) AF: 0.882 AC: 20890 AN: 23674

East Asian (EAS) AF: 0.885 AC: 34984 AN: 39548

South Asian (SAS) AF: 0.884 AC: 71071 AN: 80426

European-Finnish (FIN) AF: 0.895 AC: 42922 AN: 47940

Middle Eastern (MID) AF: 0.842 AC: 4678 AN: 5558

European-Non Finnish (NFE) AF: 0.871 AC: 956351 AN: 1098012

Other (OTH) AF: 0.864 AC: 50996 AN: 58992

GnomAD4 genome AF: 0.852 AC: 129557 AN: 152114 Hom.: 55324 Cov.: 31 AF XY: 0.853 AC XY: 63416 AN XY: 74366

African (AFR) AF: 0.803 AC: 33301 AN: 41470

American (AMR) AF: 0.843 AC: 12893 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.883 AC: 3066 AN: 3472

East Asian (EAS) AF: 0.865 AC: 4470 AN: 5168

South Asian (SAS) AF: 0.885 AC: 4258 AN: 4814

European-Finnish (FIN) AF: 0.896 AC: 9484 AN: 10588

Middle Eastern (MID) AF: 0.840 AC: 247 AN: 294

European-Non Finnish (NFE) AF: 0.872 AC: 59296 AN: 67992

Other (OTH) AF: 0.851 AC: 1796 AN: 2110

Alfa AF: 0.861 Hom.: 21419

Bravo AF: 0.847

Asia WGS AF: 0.890 AC: 3092 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	3.3
DANN	Benign	0.67
PhyloP100		-0.32
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: rs7712140; hg19: chr5-41004396;