chr5-41000090-A-T

Position:

• chr5-41000090-A-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_173489.5(MROH2B):​c.4482+130T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.438 in 1,224,304 control chromosomes in the GnomAD database, including 119,350 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 0.46 (16089 hom., cov: 32)
  • Exomes 𝑓: 0.44 (103261 hom.)
• Consequence: MROH2B NM_173489.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.164

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.51 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MROH2B	NM_173489.5	c.4482+130T>A		intron_variant		ENST00000399564.5	NP_775760.3
MROH2B	XM_011513952.2	c.4482+130T>A		intron_variant			XP_011512254.1
MROH2B	XM_011513953.2	c.4296+130T>A		intron_variant			XP_011512255.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MROH2B	ENST00000399564.5	c.4482+130T>A		intron_variant		1	NM_173489.5	ENSP00000382476	P1

Frequencies

GnomAD3 genomes AF: 0.456 AC: 69265 AN: 151930 Hom.: 16079 Cov.: 32

Gnomad AFR AF: 0.516

Gnomad AMI AF: 0.456

Gnomad AMR AF: 0.441

Gnomad ASJ AF: 0.377

Gnomad EAS AF: 0.280

Gnomad SAS AF: 0.312

Gnomad FIN AF: 0.480

Gnomad MID AF: 0.358

Gnomad NFE AF: 0.447

Gnomad OTH AF: 0.457

GnomAD4 exome AF: 0.436 AC: 467338 AN: 1072256 Hom.: 103261 Cov.: 14 AF XY: 0.432 AC XY: 232964 AN XY: 539376

Gnomad4 AFR exome AF: 0.524

Gnomad4 AMR exome AF: 0.428

Gnomad4 ASJ exome AF: 0.382

Gnomad4 EAS exome AF: 0.303

Gnomad4 SAS exome AF: 0.317

Gnomad4 FIN exome AF: 0.485

Gnomad4 NFE exome AF: 0.448

Gnomad4 OTH exome AF: 0.422

GnomAD4 genome AF: 0.456 AC: 69320 AN: 152048 Hom.: 16089 Cov.: 32 AF XY: 0.453 AC XY: 33666 AN XY: 74318

Gnomad4 AFR AF: 0.516

Gnomad4 AMR AF: 0.441

Gnomad4 ASJ AF: 0.377

Gnomad4 EAS AF: 0.281

Gnomad4 SAS AF: 0.312

Gnomad4 FIN AF: 0.480

Gnomad4 NFE AF: 0.447

Gnomad4 OTH AF: 0.452

Alfa AF: 0.463 Hom.: 2035

Bravo AF: 0.455

Asia WGS AF: 0.286 AC: 996 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	3.1
DANN	Benign	0.59

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: rs3817324; hg19: chr5-41000192; COSMIC: COSV68181083; COSMIC: COSV68181083;