rs1001420

Variant names:

• chr5-41000241-G-A
• rs1001420
• NM_173489.5:c.4461C>T

Your query was ambiguous. Multiple possible variants found:

• chr5-41000241-G-A
• chr5-41000241-G-C

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BA1

The NM_173489.5(MROH2B):​c.4461C>T​(p.Tyr1487Tyr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.681 in 1,613,428 control chromosomes in the GnomAD database, including 375,532 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 0.67 (33838 hom., cov: 31)
  • Exomes 𝑓: 0.68 (341694 hom.)
• Consequence: MROH2B NM_173489.5 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.66
• Publications: 25 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 -8 ACMG points.

• 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.4461C>T	p.Tyr1487Tyr	synonymous	Exon 39 of 42	NP_775760.3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MROH2B	ENST00000399564.5	TSL:1 MANE Select	c.4461C>T	p.Tyr1487Tyr	synonymous	Exon 39 of 42	ENSP00000382476.4	Q7Z745-1
	MROH2B	ENST00000506092.6	TSL:2	c.3126C>T	p.Tyr1042Tyr	synonymous	Exon 29 of 32	ENSP00000441504.1	F5GZ06
	MROH2B	ENST00000503890.5	TSL:2	n.3603C>T		non_coding_transcript_exon	Exon 28 of 31

Frequencies

GnomAD3 genomes AF: 0.665 AC: 101016 AN: 151886 Hom.: 33818 Cov.: 31

Gnomad AFR AF: 0.620

Gnomad AMI AF: 0.658

Gnomad AMR AF: 0.627

Gnomad ASJ AF: 0.655

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

GnomAD2 exomes AF: 0.660 AC: 164170 AN: 248640 AF XY: 0.656

Gnomad AFR exome AF: 0.619

Gnomad AMR exome AF: 0.610

Gnomad ASJ exome AF: 0.660

Gnomad EAS exome AF: 0.683

Gnomad FIN exome AF: 0.734

Gnomad NFE exome AF: 0.694

Gnomad OTH exome AF: 0.664

GnomAD4 exome AF: 0.682 AC: 996895 AN: 1461424 Hom.: 341694 Cov.: 56 AF XY: 0.678 AC XY: 493194 AN XY: 726988

African (AFR) AF: 0.623 AC: 20843 AN: 33468

American (AMR) AF: 0.613 AC: 27385 AN: 44710

Ashkenazi Jewish (ASJ) AF: 0.662 AC: 17298 AN: 26128

East Asian (EAS) AF: 0.681 AC: 27042 AN: 39694

South Asian (SAS) AF: 0.544 AC: 46929 AN: 86250

European-Finnish (FIN) AF: 0.739 AC: 39437 AN: 53400

Middle Eastern (MID) AF: 0.679 AC: 3917 AN: 5768

European-Non Finnish (NFE) AF: 0.696 AC: 773521 AN: 1111644

Other (OTH) AF: 0.671 AC: 40523 AN: 60362

GnomAD4 genome AF: 0.665 AC: 101089 AN: 152004 Hom.: 33838 Cov.: 31 AF XY: 0.663 AC XY: 49308 AN XY: 74320

African (AFR) AF: 0.620 AC: 25717 AN: 41458

American (AMR) AF: 0.627 AC: 9575 AN: 15266

Ashkenazi Jewish (ASJ) AF: 0.655 AC: 2272 AN: 3470

East Asian (EAS) AF: 0.676 AC: 3481 AN: 5152

South Asian (SAS) AF: 0.558 AC: 2684 AN: 4814

European-Finnish (FIN) AF: 0.736 AC: 7786 AN: 10574

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

European-Non Finnish (NFE) AF: 0.697 AC: 47372 AN: 67952

Other (OTH) AF: 0.668 AC: 1412 AN: 2114

Alfa AF: 0.677 Hom.: 91064

Bravo AF: 0.657

Asia WGS AF: 0.620 AC: 2157 AN: 3478

EpiCase AF: 0.687

EpiControl AF: 0.683

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.027
DANN	Benign	0.26
PhyloP100		-1.7
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.25		Details are displayed if max score is > 0.2
DS_DL_spliceai		0.25		Position offset: -21

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs1001420; hg19: chr5-41000343; COSMIC: COSV68181090; COSMIC: COSV68181090;