5-41000090-A-T

Variant names:

• chr5-41000090-A-T
• rs3817324
• NM_173489.5:c.4482+130T>A

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 2 publications found

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]

C7 Gene-Disease associations (from GenCC):

• complement component 7 deficiency

  Inheritance: AR Classification: STRONG Submitted by: Ambry Genetics, Illumina, Labcorp Genetics (formerly Invitae)

ACMG classification

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_173489.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MROH2B	NM_173489.5	MANE Select	c.4482+130T>A		intron	N/A	NP_775760.3

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MROH2B	ENST00000399564.5	TSL:1 MANE Select	c.4482+130T>A		intron	N/A	ENSP00000382476.4
	MROH2B	ENST00000506092.6	TSL:2	c.3147+130T>A		intron	N/A	ENSP00000441504.1
	MROH2B	ENST00000503890.5	TSL:2	n.3624+130T>A		intron	N/A

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

African (AFR) AF: 0.524 AC: 12956 AN: 24728

American (AMR) AF: 0.428 AC: 12209 AN: 28516

Ashkenazi Jewish (ASJ) AF: 0.382 AC: 6967 AN: 18238

East Asian (EAS) AF: 0.303 AC: 11334 AN: 37402

South Asian (SAS) AF: 0.317 AC: 20148 AN: 63492

European-Finnish (FIN) AF: 0.485 AC: 23596 AN: 48698

Middle Eastern (MID) AF: 0.424 AC: 1332 AN: 3144

European-Non Finnish (NFE) AF: 0.448 AC: 358992 AN: 801144

Other (OTH) AF: 0.422 AC: 19804 AN: 46894

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

African (AFR) AF: 0.516 AC: 21402 AN: 41486

American (AMR) AF: 0.441 AC: 6737 AN: 15268

Ashkenazi Jewish (ASJ) AF: 0.377 AC: 1307 AN: 3470

East Asian (EAS) AF: 0.281 AC: 1455 AN: 5172

South Asian (SAS) AF: 0.312 AC: 1499 AN: 4806

European-Finnish (FIN) AF: 0.480 AC: 5086 AN: 10586

Middle Eastern (MID) AF: 0.344 AC: 101 AN: 294

European-Non Finnish (NFE) AF: 0.447 AC: 30366 AN: 67948

Other (OTH) AF: 0.452 AC: 953 AN: 2110

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 v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	3.1
DANN	Benign	0.59
PhyloP100		0.16
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

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