5-40998094-T-C

Position:

• chr5-40998094-T-C

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

The NM_173489.5(MROH2B):​c.4716A>G​(p.Gln1572=) 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

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 -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MROH2B	NM_173489.5	c.4716A>G	p.Gln1572=	synonymous_variant	42/42	ENST00000399564.5	NP_775760.3
MROH2B	XM_011513953.2	c.4530A>G	p.Gln1510=	synonymous_variant	41/41		XP_011512255.1
MROH2B	XM_011513952.2	c.*81A>G		3_prime_UTR_variant	43/43		XP_011512254.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MROH2B	ENST00000399564.5	c.4716A>G	p.Gln1572=	synonymous_variant	42/42	1	NM_173489.5	ENSP00000382476	P1

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

GnomAD3 exomes AF: 0.634 AC: 156568 AN: 246822 Hom.: 50265 AF XY: 0.630 AC XY: 84302 AN XY: 133896

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 SAS exome AF: 0.538

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

Gnomad4 AFR exome AF: 0.614

Gnomad4 AMR exome AF: 0.589

Gnomad4 ASJ exome AF: 0.603

Gnomad4 EAS exome AF: 0.692

Gnomad4 SAS exome AF: 0.535

Gnomad4 FIN exome AF: 0.720

Gnomad4 NFE exome AF: 0.657

Gnomad4 OTH exome AF: 0.639

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

Gnomad4 AFR AF: 0.611

Gnomad4 AMR AF: 0.595

Gnomad4 ASJ AF: 0.594

Gnomad4 EAS AF: 0.689

Gnomad4 SAS AF: 0.551

Gnomad4 FIN AF: 0.719

Gnomad4 NFE AF: 0.659

Gnomad4 OTH AF: 0.620

Alfa AF: 0.647 Hom.: 62088

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 v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.61
CADD	Benign	7.2
DANN	Benign	0.69

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: rs704040; hg19: chr5-40998196; COSMIC: COSV68183320;