5-41000921-G-A

Variant names:

• chr5-41000921-G-A
• rs2167229
• NM_173489.5:c.4195-88C>T

Variant summary

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

The NM_173489.5(MROH2B):​c.4195-88C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.682 in 1,405,224 control chromosomes in the GnomAD database, including 328,856 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 0.66 (33550 hom., cov: 30)
  • Exomes 𝑓: 0.68 (295306 hom.)
• Consequence: MROH2B NM_173489.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.829
• 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: Illumina, Ambry Genetics, Labcorp Genetics (formerly Invitae)

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.692 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MROH2B	NM_173489.5	MANE Select	c.4195-88C>T		intron	N/A	NP_775760.3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MROH2B	ENST00000399564.5	TSL:1 MANE Select	c.4195-88C>T		intron	N/A	ENSP00000382476.4	Q7Z745-1
	MROH2B	ENST00000506092.6	TSL:2	c.2860-88C>T		intron	N/A	ENSP00000441504.1	F5GZ06
	MROH2B	ENST00000503890.5	TSL:2	n.3337-88C>T		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.663 AC: 100520 AN: 151710 Hom.: 33530 Cov.: 30

Gnomad AFR AF: 0.612

Gnomad AMI AF: 0.660

Gnomad AMR AF: 0.626

Gnomad ASJ AF: 0.654

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

GnomAD4 exome AF: 0.685 AC: 858207 AN: 1253396 Hom.: 295306 AF XY: 0.681 AC XY: 417311 AN XY: 612614

African (AFR) AF: 0.612 AC: 16632 AN: 27192

American (AMR) AF: 0.619 AC: 13075 AN: 21108

Ashkenazi Jewish (ASJ) AF: 0.661 AC: 12665 AN: 19168

East Asian (EAS) AF: 0.685 AC: 24019 AN: 35076

South Asian (SAS) AF: 0.542 AC: 33624 AN: 62008

European-Finnish (FIN) AF: 0.738 AC: 33910 AN: 45976

Middle Eastern (MID) AF: 0.680 AC: 3367 AN: 4952

European-Non Finnish (NFE) AF: 0.696 AC: 685872 AN: 985734

Other (OTH) AF: 0.672 AC: 35043 AN: 52182

GnomAD4 genome AF: 0.663 AC: 100593 AN: 151828 Hom.: 33550 Cov.: 30 AF XY: 0.661 AC XY: 49070 AN XY: 74218

African (AFR) AF: 0.612 AC: 25281 AN: 41332

American (AMR) AF: 0.626 AC: 9550 AN: 15254

Ashkenazi Jewish (ASJ) AF: 0.654 AC: 2269 AN: 3468

East Asian (EAS) AF: 0.676 AC: 3484 AN: 5154

South Asian (SAS) AF: 0.558 AC: 2683 AN: 4810

European-Finnish (FIN) AF: 0.736 AC: 7771 AN: 10558

Middle Eastern (MID) AF: 0.650 AC: 191 AN: 294

European-Non Finnish (NFE) AF: 0.697 AC: 47358 AN: 67942

Other (OTH) AF: 0.667 AC: 1408 AN: 2110

Alfa AF: 0.639 Hom.: 3423

Bravo AF: 0.654

Asia WGS AF: 0.620 AC: 2156 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	1.1
DANN	Benign	0.69
PhyloP100		-0.83
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: rs2167229; hg19: chr5-41001023; COSMIC: COSV68183325; COSMIC: COSV68183325;