5-40998094-T-C

Variant names:

• chr5-40998094-T-C
• rs704040
• NM_173489.5:c.4716A>G

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

The NM_173489.5(MROH2B):​c.4716A>G​(p.Gln1572Gln) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.647 in 1,605,046 control chromosomes in the GnomAD database, including 338,323 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 0.64 (31214 hom., cov: 33)
  • Exomes 𝑓: 0.65 (307109 hom.)
• Consequence: MROH2B NM_173489.5 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.39
• Publications: 18 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 -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.61).
• BP7: Synonymous conserved (PhyloP=1.39 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.67 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.4716A>G	p.Gln1572Gln	synonymous	Exon 42 of 42	NP_775760.3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MROH2B	ENST00000399564.5	TSL:1 MANE Select	c.4716A>G	p.Gln1572Gln	synonymous	Exon 42 of 42	ENSP00000382476.4	Q7Z745-1
	MROH2B	ENST00000511934.5	TSL:1	n.523A>G		non_coding_transcript_exon	Exon 3 of 3
	MROH2B	ENST00000506092.6	TSL:2	c.3381A>G	p.Gln1127Gln	synonymous	Exon 32 of 32	ENSP00000441504.1	F5GZ06

Frequencies

GnomAD3 genomes AF: 0.639 AC: 97071 AN: 151980 Hom.: 31192 Cov.: 33

Gnomad AFR AF: 0.611

Gnomad AMI AF: 0.587

Gnomad AMR AF: 0.595

Gnomad ASJ AF: 0.594

Gnomad EAS AF: 0.687

Gnomad SAS AF: 0.552

Gnomad FIN AF: 0.719

Gnomad MID AF: 0.630

Gnomad NFE AF: 0.659

Gnomad OTH AF: 0.620

GnomAD2 exomes AF: 0.634 AC: 156568 AN: 246822 AF XY: 0.630

Gnomad AFR exome AF: 0.610

Gnomad AMR exome AF: 0.586

Gnomad ASJ exome AF: 0.600

Gnomad EAS exome AF: 0.699

Gnomad FIN exome AF: 0.717

Gnomad NFE exome AF: 0.656

Gnomad OTH exome AF: 0.629

GnomAD4 exome AF: 0.648 AC: 941316 AN: 1452948 Hom.: 307109 Cov.: 36 AF XY: 0.645 AC XY: 465956 AN XY: 722954

African (AFR) AF: 0.614 AC: 20408 AN: 33220

American (AMR) AF: 0.589 AC: 26013 AN: 44188

Ashkenazi Jewish (ASJ) AF: 0.603 AC: 15679 AN: 25994

East Asian (EAS) AF: 0.692 AC: 27370 AN: 39560

South Asian (SAS) AF: 0.535 AC: 45789 AN: 85564

European-Finnish (FIN) AF: 0.720 AC: 38301 AN: 53228

Middle Eastern (MID) AF: 0.615 AC: 3532 AN: 5740

European-Non Finnish (NFE) AF: 0.657 AC: 725833 AN: 1105416

Other (OTH) AF: 0.639 AC: 38391 AN: 60038

GnomAD4 genome AF: 0.639 AC: 97147 AN: 152098 Hom.: 31214 Cov.: 33 AF XY: 0.638 AC XY: 47438 AN XY: 74380

African (AFR) AF: 0.611 AC: 25311 AN: 41454

American (AMR) AF: 0.595 AC: 9096 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.594 AC: 2060 AN: 3470

East Asian (EAS) AF: 0.689 AC: 3561 AN: 5172

South Asian (SAS) AF: 0.551 AC: 2660 AN: 4826

European-Finnish (FIN) AF: 0.719 AC: 7611 AN: 10592

Middle Eastern (MID) AF: 0.612 AC: 180 AN: 294

European-Non Finnish (NFE) AF: 0.659 AC: 44822 AN: 67976

Other (OTH) AF: 0.620 AC: 1312 AN: 2116

Alfa AF: 0.643 Hom.: 93286

Bravo AF: 0.629

Asia WGS AF: 0.621 AC: 2158 AN: 3478

EpiCase AF: 0.649

EpiControl AF: 0.640

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.61
CADD	Benign	7.2
DANN	Benign	0.69
PhyloP100		1.4
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: rs704040; hg19: chr5-40998196; COSMIC: COSV68183320;