rs1450658

Variant names:

• chr5-41009140-C-T
• rs1450658
• NM_173489.5:c.3420+140G>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.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
• Publications: 4 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: Illumina, Ambry Genetics, Labcorp Genetics (formerly Invitae)

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.857 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_173489.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MROH2B	NM_173489.5	MANE Select	c.3420+140G>A		intron	N/A	NP_775760.3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MROH2B	ENST00000399564.5	TSL:1 MANE Select	c.3420+140G>A		intron	N/A	ENSP00000382476.4	Q7Z745-1
	MROH2B	ENST00000506092.6	TSL:2	c.2085+140G>A		intron	N/A	ENSP00000441504.1	F5GZ06
	MROH2B	ENST00000503890.5	TSL:2	n.2382+140G>A		intron	N/A

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

African (AFR) AF: 0.869 AC: 21328 AN: 24554

American (AMR) AF: 0.848 AC: 20203 AN: 23814

Ashkenazi Jewish (ASJ) AF: 0.786 AC: 13555 AN: 17238

East Asian (EAS) AF: 0.632 AC: 23019 AN: 36414

South Asian (SAS) AF: 0.796 AC: 42723 AN: 53672

European-Finnish (FIN) AF: 0.773 AC: 29898 AN: 38686

Middle Eastern (MID) AF: 0.815 AC: 2491 AN: 3058

European-Non Finnish (NFE) AF: 0.825 AC: 670293 AN: 812364

Other (OTH) AF: 0.805 AC: 36815 AN: 45724

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

African (AFR) AF: 0.865 AC: 35886 AN: 41504

American (AMR) AF: 0.861 AC: 13151 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.797 AC: 2768 AN: 3472

East Asian (EAS) AF: 0.620 AC: 3204 AN: 5166

South Asian (SAS) AF: 0.782 AC: 3770 AN: 4818

European-Finnish (FIN) AF: 0.765 AC: 8067 AN: 10546

Middle Eastern (MID) AF: 0.759 AC: 223 AN: 294

European-Non Finnish (NFE) AF: 0.821 AC: 55854 AN: 67996

Other (OTH) AF: 0.820 AC: 1734 AN: 2114

Alfa AF: 0.822 Hom.: 28890

Bravo AF: 0.830

Asia WGS AF: 0.664 AC: 2308 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	2.0
DANN	Benign	0.22
PhyloP100		0.13
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: rs1450658; hg19: chr5-41009242; COSMIC: COSV68183691;