Variant chr5-41000921-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_173489.5(MROH2B):c.4195-88C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.682 in 1,405,224 control chromosomes in the GnomAD database, including 328,856 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 0.66 ( 33550 hom., cov: 30)

Exomes 𝑓: 0.68 ( 295306 hom. )

Consequence

MROH2B
NM_173489.5 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.829

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 -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.84).

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.692 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	MANE	Protein
MROH2B	NM_173489.5 link	c.4195-88C>T	intron_variant	ENST00000399564.5	NP_775760.3
MROH2B	XM_011513952.2 link	c.4195-88C>T	intron_variant		XP_011512254.1
MROH2B	XM_011513953.2 link	c.4009-88C>T	intron_variant		XP_011512255.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MROH2B	ENST00000399564.5 link	c.4195-88C>T		intron_variant		1	NM_173489.5	ENSP00000382476.4		Q7Z745-1

Frequencies

GnomAD3 genomes

AF:

0.663

AC:

100520

AN:

151710

Hom.:

33530

Cov.:

show subpopulations

Gnomad AFR

AF:

0.612

Gnomad AMI

AF:

0.660

Gnomad AMR

AF:

0.626

Gnomad ASJ

AF:

0.654

Gnomad EAS

AF:

0.675

Gnomad SAS

AF:

0.559

Gnomad FIN

AF:

0.736

Gnomad MID

AF:

0.665

Gnomad NFE

AF:

0.697

Gnomad OTH

AF:

0.668

GnomAD4 exome

AF:

0.685

AC:

858207

AN:

1253396

Hom.:

295306

AF XY:

0.681

AC XY:

417311

AN XY:

612614

show subpopulations

Gnomad4 AFR exome

AF:

0.612

Gnomad4 AMR exome

AF:

0.619

Gnomad4 ASJ exome

AF:

0.661

Gnomad4 EAS exome

AF:

0.685

Gnomad4 SAS exome

AF:

0.542

Gnomad4 FIN exome

AF:

0.738

Gnomad4 NFE exome

AF:

0.696

Gnomad4 OTH exome

AF:

0.672

GnomAD4 genome

AF:

0.663

AC:

100593

AN:

151828

Hom.:

33550

Cov.:

AF XY:

0.661

AC XY:

49070

AN XY:

74218

show subpopulations

Gnomad4 AFR

AF:

0.612

Gnomad4 AMR

AF:

0.626

Gnomad4 ASJ

AF:

0.654

Gnomad4 EAS

AF:

0.676

Gnomad4 SAS

AF:

0.558

Gnomad4 FIN

AF:

0.736

Gnomad4 NFE

AF:

0.697

Gnomad4 OTH

AF:

0.667

Alfa

AF:

0.639

Hom.:

3423

Bravo

AF:

0.654

Asia WGS

AF:

0.620

AC:

2156

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.84

CADD

Benign

1.1

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

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