rs1001420

chr5-41000241-G-Achr5-41000241-G-C

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BA1

The NM_173489.5(MROH2B):c.4461C>T(p.Tyr1487=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.681 in 1,613,428 control chromosomes in the GnomAD database, including 375,532 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 0.67 (33838 hom., cov: 31)
  • Exomes 𝑓: 0.68 (341694 hom.)
• Consequence: MROH2B NM_173489.5 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.66

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 -8 ACMG points.

• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.692 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MROH2B	NM_173489.5	c.4461C>T	p.Tyr1487=	synonymous_variant	39/42	ENST00000399564.5
MROH2B	XM_011513952.2	c.4461C>T	p.Tyr1487=	synonymous_variant	39/43
MROH2B	XM_011513953.2	c.4275C>T	p.Tyr1425=	synonymous_variant	38/41

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MROH2B	ENST00000399564.5	c.4461C>T	p.Tyr1487=	synonymous_variant	39/42	1	NM_173489.5	P1

Frequencies

GnomAD3 genomes AF: 0.665 AC: 101016 AN: 151886 Hom.: 33818 Cov.: 31

Gnomad AFR AF: 0.620

Gnomad AMI AF: 0.658

Gnomad AMR AF: 0.627

Gnomad ASJ AF: 0.655

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

GnomAD3 exomes AF: 0.660 AC: 164170 AN: 248640 Hom.: 54731 AF XY: 0.656 AC XY: 88457 AN XY: 134854

Gnomad AFR exome AF: 0.619

Gnomad AMR exome AF: 0.610

Gnomad ASJ exome AF: 0.660

Gnomad EAS exome AF: 0.683

Gnomad SAS exome AF: 0.547

Gnomad FIN exome AF: 0.734

Gnomad NFE exome AF: 0.694

Gnomad OTH exome AF: 0.664

GnomAD4 exome AF: 0.682 AC: 996895 AN: 1461424 Hom.: 341694 Cov.: 56 AF XY: 0.678 AC XY: 493194 AN XY: 726988

Gnomad4 AFR exome AF: 0.623

Gnomad4 AMR exome AF: 0.613

Gnomad4 ASJ exome AF: 0.662

Gnomad4 EAS exome AF: 0.681

Gnomad4 SAS exome AF: 0.544

Gnomad4 FIN exome AF: 0.739

Gnomad4 NFE exome AF: 0.696

Gnomad4 OTH exome AF: 0.671

GnomAD4 genome AF: 0.665 AC: 101089 AN: 152004 Hom.: 33838 Cov.: 31 AF XY: 0.663 AC XY: 49308 AN XY: 74320

Gnomad4 AFR AF: 0.620

Gnomad4 AMR AF: 0.627

Gnomad4 ASJ AF: 0.655

Gnomad4 EAS AF: 0.676

Gnomad4 SAS AF: 0.558

Gnomad4 FIN AF: 0.736

Gnomad4 NFE AF: 0.697

Gnomad4 OTH AF: 0.668

Alfa AF: 0.681 Hom.: 57887

Bravo AF: 0.657

Asia WGS AF: 0.620 AC: 2157 AN: 3478

EpiCase AF: 0.687

EpiControl AF: 0.683

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
Cadd	Benign	0.027
Dann	Benign	0.26

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.25		Details are displayed if max score is > 0.2
DS_DL_spliceai		0.25		Position offset: -21

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs1001420; hg19: chr5-41000343; COSMIC: COSV68181090; COSMIC: COSV68181090;