Variant 5-41000741-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -11 ACMG points: 0P and 11B. BP4_StrongBP6_ModerateBP7BS2

The ENST00000399564.5(MROH2B):c.4287A>G(p.Glu1429=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000433 in 1,611,892 control chromosomes in the GnomAD database, including 6 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.00018 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00046 ( 6 hom. )

Consequence

MROH2B
ENST00000399564.5 synonymous

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.555

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=-0.53).

BP6

Variant 5-41000741-T-C is Benign according to our data. Variant chr5-41000741-T-C is described in ClinVar as [Likely_benign]. Clinvar id is 2655446.Status of the report is criteria_provided_single_submitter, 1 stars.

BP7

Synonymous conserved (PhyloP=0.555 with no splicing effect.

BS2

High Homozygotes in GnomAdExome4 at 6 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
MROH2B	NM_173489.5 linkuse as main transcript	c.4287A>G	p.Glu1429=	synonymous_variant	38/42	ENST00000399564.5	NP_775760.3
MROH2B	XM_011513952.2 linkuse as main transcript	c.4287A>G	p.Glu1429=	synonymous_variant	38/43		XP_011512254.1
MROH2B	XM_011513953.2 linkuse as main transcript	c.4101A>G	p.Glu1367=	synonymous_variant	37/41		XP_011512255.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MROH2B	ENST00000399564.5 linkuse as main transcript	c.4287A>G	p.Glu1429=	synonymous_variant	38/42	1	NM_173489.5	ENSP00000382476	P1	Q7Z745-1

Frequencies

GnomAD3 genomes

AF:

0.000184

AC:

AN:

152012

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000483

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00374

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000118

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000841

AC:

205

AN:

243750

Hom.:

AF XY:

0.00113

AC XY:

149

AN XY:

132092

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.000101

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00647

Gnomad FIN exome

AF:

0.000141

Gnomad NFE exome

AF:

0.0000636

Gnomad OTH exome

AF:

0.000338

GnomAD4 exome

AF:

0.000459

AC:

670

AN:

1459762

Hom.:

Cov.:

AF XY:

0.000642

AC XY:

466

AN XY:

725908

show subpopulations

Gnomad4 AFR exome

AF:

0.0000299

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000252

Gnomad4 SAS exome

AF:

0.00626

Gnomad4 FIN exome

AF:

0.000113

Gnomad4 NFE exome

AF:

0.0000630

Gnomad4 OTH exome

AF:

0.000498

GnomAD4 genome

AF:

0.000184

AC:

AN:

152130

Hom.:

Cov.:

AF XY:

0.000229

AC XY:

AN XY:

74370

show subpopulations

Gnomad4 AFR

AF:

0.0000482

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00374

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000118

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000122

Hom.:

Bravo

AF:

0.000125

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Oct 01, 2022

MROH2B: BP4, BP7 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.53

CADD

Benign

8.0

DANN

Benign

0.56

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over