NM_173489.5:c.4011+69G>A

Variant names:

• chr5-41004705-C-T
• rs2305314
• NM_173489.5:c.4011+69G>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.4011+69G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.615 in 1,565,310 control chromosomes in the GnomAD database, including 298,169 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 0.61 (28585 hom., cov: 32)
  • Exomes 𝑓: 0.62 (269584 hom.)
• Consequence: MROH2B NM_173489.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.03
• 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=-0.94).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.698 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MROH2B	NM_173489.5	MANE Select	c.4011+69G>A		intron	N/A	NP_775760.3

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MROH2B	ENST00000399564.5	TSL:1 MANE Select	c.4011+69G>A		intron	N/A	ENSP00000382476.4
	MROH2B	ENST00000506092.6	TSL:2	c.2676+69G>A		intron	N/A	ENSP00000441504.1
	MROH2B	ENST00000503890.5	TSL:2	n.3153+69G>A		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.611 AC: 92816 AN: 151914 Hom.: 28565 Cov.: 32

Gnomad AFR AF: 0.586

Gnomad AMI AF: 0.643

Gnomad AMR AF: 0.583

Gnomad ASJ AF: 0.612

Gnomad EAS AF: 0.716

Gnomad SAS AF: 0.487

Gnomad FIN AF: 0.664

Gnomad MID AF: 0.579

Gnomad NFE AF: 0.625

Gnomad OTH AF: 0.620

GnomAD4 exome AF: 0.616 AC: 870465 AN: 1413278 Hom.: 269584 Cov.: 31 AF XY: 0.612 AC XY: 427809 AN XY: 698658

African (AFR) AF: 0.592 AC: 18840 AN: 31810

American (AMR) AF: 0.584 AC: 22176 AN: 37952

Ashkenazi Jewish (ASJ) AF: 0.621 AC: 14289 AN: 23026

East Asian (EAS) AF: 0.729 AC: 28630 AN: 39296

South Asian (SAS) AF: 0.476 AC: 37082 AN: 77922

European-Finnish (FIN) AF: 0.668 AC: 34376 AN: 51428

Middle Eastern (MID) AF: 0.601 AC: 2502 AN: 4164

European-Non Finnish (NFE) AF: 0.622 AC: 677142 AN: 1089460

Other (OTH) AF: 0.609 AC: 35428 AN: 58220

GnomAD4 genome AF: 0.611 AC: 92886 AN: 152032 Hom.: 28585 Cov.: 32 AF XY: 0.610 AC XY: 45352 AN XY: 74332

African (AFR) AF: 0.586 AC: 24275 AN: 41450

American (AMR) AF: 0.583 AC: 8904 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.612 AC: 2123 AN: 3468

East Asian (EAS) AF: 0.717 AC: 3693 AN: 5150

South Asian (SAS) AF: 0.486 AC: 2340 AN: 4814

European-Finnish (FIN) AF: 0.664 AC: 7035 AN: 10592

Middle Eastern (MID) AF: 0.561 AC: 165 AN: 294

European-Non Finnish (NFE) AF: 0.625 AC: 42454 AN: 67962

Other (OTH) AF: 0.621 AC: 1311 AN: 2112

Alfa AF: 0.621 Hom.: 11453

Bravo AF: 0.606

Asia WGS AF: 0.605 AC: 2102 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	4.6
DANN	Benign	0.40
PhyloP100		1.0
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: rs2305314; hg19: chr5-41004807; COSMIC: COSV68181097; COSMIC: COSV68181097;