rs3817324

Variant names:

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

Your query was ambiguous. Multiple possible variants found:

• chr5-41000090-A-C
• chr5-41000090-A-G
• chr5-41000090-A-T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_173489.5(MROH2B):​c.4482+130T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000093 in 1,075,066 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: not found (cov: 32)
  • Exomes 𝑓: 9.3e-7 (0 hom.)
• Consequence: MROH2B NM_173489.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.164
• Publications: 0 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MROH2B	NM_173489.5	c.4482+130T>G		intron_variant	Intron 39 of 41	ENST00000399564.5	NP_775760.3
MROH2B	XM_011513952.2	c.4482+130T>G		intron_variant	Intron 39 of 42		XP_011512254.1
MROH2B	XM_011513953.2	c.4296+130T>G		intron_variant	Intron 38 of 40		XP_011512255.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MROH2B	ENST00000399564.5	c.4482+130T>G		intron_variant	Intron 39 of 41	1	NM_173489.5	ENSP00000382476.4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 9.30e-7 AC: 1 AN: 1075066 Hom.: 0 Cov.: 14 AF XY: 0.00000185 AC XY: 1 AN XY: 540784

African (AFR) AF: 0.00 AC: 0 AN: 24770

American (AMR) AF: 0.00 AC: 0 AN: 28564

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 18270

East Asian (EAS) AF: 0.00 AC: 0 AN: 37442

South Asian (SAS) AF: 0.00 AC: 0 AN: 63584

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 48776

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3146

European-Non Finnish (NFE) AF: 0.00000124 AC: 1 AN: 803528

Other (OTH) AF: 0.00 AC: 0 AN: 46986

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	3.2
DANN	Benign	0.53
PhyloP100		0.16

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;