rs1530812

Variant names:

• chr5-41000050-G-A
• rs1530812
• ENST00000511934.5:n.19C>T

Your query was ambiguous. Multiple possible variants found:

• chr5-41000050-G-A
• chr5-41000050-G-T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000511934.5(MROH2B):​n.19C>T variant causes a non coding transcript exon change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.506 in 861,718 control chromosomes in the GnomAD database, including 110,972 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 0.48 (17644 hom., cov: 33)
  • Exomes 𝑓: 0.51 (93328 hom.)
• Consequence: MROH2B ENST00000511934.5 non_coding_transcript_exon
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.83
• Publications: 4 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=-0.85).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.606 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MROH2B	NM_173489.5	c.4482+170C>T		intron_variant	Intron 39 of 41	ENST00000399564.5	NP_775760.3
MROH2B	XM_011513952.2	c.4482+170C>T		intron_variant	Intron 39 of 42		XP_011512254.1
MROH2B	XM_011513953.2	c.4296+170C>T		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+170C>T		intron_variant	Intron 39 of 41	1	NM_173489.5	ENSP00000382476.4

Frequencies

GnomAD3 genomes AF: 0.478 AC: 72641 AN: 151998 Hom.: 17628 Cov.: 33

Gnomad AFR AF: 0.420

Gnomad AMI AF: 0.381

Gnomad AMR AF: 0.459

Gnomad ASJ AF: 0.562

Gnomad EAS AF: 0.587

Gnomad SAS AF: 0.625

Gnomad FIN AF: 0.473

Gnomad MID AF: 0.576

Gnomad NFE AF: 0.496

Gnomad OTH AF: 0.464

GnomAD4 exome AF: 0.511 AC: 362936 AN: 709600 Hom.: 93328 Cov.: 9 AF XY: 0.516 AC XY: 186526 AN XY: 361718

African (AFR) AF: 0.420 AC: 7301 AN: 17382

American (AMR) AF: 0.468 AC: 9132 AN: 19496

Ashkenazi Jewish (ASJ) AF: 0.555 AC: 8453 AN: 15244

East Asian (EAS) AF: 0.582 AC: 19154 AN: 32904

South Asian (SAS) AF: 0.618 AC: 31154 AN: 50444

European-Finnish (FIN) AF: 0.472 AC: 19953 AN: 42236

Middle Eastern (MID) AF: 0.487 AC: 1190 AN: 2444

European-Non Finnish (NFE) AF: 0.503 AC: 248764 AN: 494930

Other (OTH) AF: 0.517 AC: 17835 AN: 34520

GnomAD4 genome AF: 0.478 AC: 72702 AN: 152118 Hom.: 17644 Cov.: 33 AF XY: 0.480 AC XY: 35665 AN XY: 74358

African (AFR) AF: 0.420 AC: 17422 AN: 41482

American (AMR) AF: 0.459 AC: 7020 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.562 AC: 1951 AN: 3472

East Asian (EAS) AF: 0.586 AC: 3028 AN: 5164

South Asian (SAS) AF: 0.625 AC: 3011 AN: 4820

European-Finnish (FIN) AF: 0.473 AC: 5014 AN: 10590

Middle Eastern (MID) AF: 0.585 AC: 172 AN: 294

European-Non Finnish (NFE) AF: 0.496 AC: 33749 AN: 67992

Other (OTH) AF: 0.468 AC: 990 AN: 2114

Alfa AF: 0.495 Hom.: 11713

Bravo AF: 0.475

Asia WGS AF: 0.623 AC: 2165 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	8.4
DANN	Benign	0.20
PhyloP100		1.8
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs1530812; hg19: chr5-41000152; COSMIC: COSV68182126;