Variant 5-40998133-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -11 ACMG points: 0P and 11B. BP4_ModerateBP7BA1

The ENST00000399564.5(MROH2B):c.4677G>A(p.Pro1559=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.39 in 1,600,780 control chromosomes in the GnomAD database, including 124,677 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 0.37 ( 10793 hom., cov: 32)

Exomes 𝑓: 0.39 ( 113884 hom. )

Consequence

MROH2B
ENST00000399564.5 synonymous

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.636

Variant links:

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]

MROH2B links:

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 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -11 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.45).

BP7

Synonymous conserved (PhyloP=-0.636 with no splicing effect.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.404 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
MROH2B	NM_173489.5 linkuse as main transcript	c.4677G>A	p.Pro1559=	synonymous_variant	42/42	ENST00000399564.5	NP_775760.3
MROH2B	XM_011513953.2 linkuse as main transcript	c.4491G>A	p.Pro1497=	synonymous_variant	41/41		XP_011512255.1
MROH2B	XM_011513952.2 linkuse as main transcript	c.*42G>A		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 linkuse as main transcript	c.4677G>A	p.Pro1559=	synonymous_variant	42/42	1	NM_173489.5	ENSP00000382476	P1	Q7Z745-1

Frequencies

GnomAD3 genomes

AF:

0.372

AC:

56518

AN:

151924

Hom.:

10788

Cov.:

show subpopulations

Gnomad AFR

AF:

0.309

Gnomad AMI

AF:

0.380

Gnomad AMR

AF:

0.383

Gnomad ASJ

AF:

0.315

Gnomad EAS

AF:

0.291

Gnomad SAS

AF:

0.304

Gnomad FIN

AF:

0.463

Gnomad MID

AF:

0.298

Gnomad NFE

AF:

0.408

Gnomad OTH

AF:

0.367

GnomAD3 exomes

AF:

0.375

AC:

92438

AN:

246424

Hom.:

17969

AF XY:

0.372

AC XY:

49709

AN XY:

133680

show subpopulations

Gnomad AFR exome

AF:

0.308

Gnomad AMR exome

AF:

0.382

Gnomad ASJ exome

AF:

0.315

Gnomad EAS exome

AF:

0.297

Gnomad SAS exome

AF:

0.311

Gnomad FIN exome

AF:

0.468

Gnomad NFE exome

AF:

0.400

Gnomad OTH exome

AF:

0.370

GnomAD4 exome

AF:

0.392

AC:

567747

AN:

1448736

Hom.:

113884

Cov.:

AF XY:

0.390

AC XY:

280873

AN XY:

721066

show subpopulations

Gnomad4 AFR exome

AF:

0.307

Gnomad4 AMR exome

AF:

0.382

Gnomad4 ASJ exome

AF:

0.320

Gnomad4 EAS exome

AF:

0.312

Gnomad4 SAS exome

AF:

0.306

Gnomad4 FIN exome

AF:

0.465

Gnomad4 NFE exome

AF:

0.404

Gnomad4 OTH exome

AF:

0.372

GnomAD4 genome

AF:

0.372

AC:

56545

AN:

152044

Hom.:

10793

Cov.:

AF XY:

0.373

AC XY:

27712

AN XY:

74320

show subpopulations

Gnomad4 AFR

AF:

0.309

Gnomad4 AMR

AF:

0.384

Gnomad4 ASJ

AF:

0.315

Gnomad4 EAS

AF:

0.293

Gnomad4 SAS

AF:

0.304

Gnomad4 FIN

AF:

0.463

Gnomad4 NFE

AF:

0.408

Gnomad4 OTH

AF:

0.362

Alfa

AF:

0.380

Hom.:

15070

Bravo

AF:

0.362

Asia WGS

AF:

0.271

AC:

942

AN:

3478

EpiCase

AF:

0.401

EpiControl

AF:

0.397

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.45

CADD

Benign

0.39

DANN

Benign

0.36

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over