1-156381908-G-A

Variant names:

• chr1-156381908-G-A
• rs3748569
• NM_020407.5:c.943G>A
• RHBG p.Gly315Arg

Variant summary

Our verdict is Benign. The variant received -11 ACMG points: 1P and 12B. PP3 BP4_Strong BA1

The NM_020407.5(RHBG):​c.943G>A​(p.Gly315Arg) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.45 in 1,609,256 control chromosomes in the GnomAD database, including 165,875 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 (18171 hom., cov: 31)
  • Exomes 𝑓: 0.45 (147704 hom.)
• Consequence: RHBG NM_020407.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 7.76
• Publications: 28 publications found

Genes affected

RHBG (HGNC:14572): (Rh family B glycoprotein) This gene encodes one of two non-erythroid members of the Rhesus (Rh) protein family. Non-erythroid Rh protein family members are mainly expressed in the kidney and belong to the methylammonium-ammonium permease/ammonia transporters superfamily. All Rh family proteins are predicted to be transmembrane proteins with 12 membrane spanning domains and intracytoplasmic N- and C-termini. Alternative splicing of this gene results in multiple transcript variants. [provided by RefSeq, Jan 2012]

ACMG classification

Our verdict: Benign. The variant received -11 ACMG points.

• PP3: Multiple lines of computational evidence support a deleterious effect 6: AlphaMissense, BayesDel_noAF, Cadd, Dann, Eigen, phyloP100way_vertebrate [when BayesDel_addAF, max_spliceai, MetaRNN, MutationTaster was below the threshold]
• BP4: Computational evidence support a benign effect (MetaRNN=3.0048128E-5).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.679 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_020407.5. 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
	RHBG	NM_020407.5	MANE Select	c.943G>A	p.Gly315Arg	missense	Exon 6 of 10	NP_065140.3	Q9H310-1
	RHBG	NM_001256396.2		c.853G>A	p.Gly285Arg	missense	Exon 7 of 11	NP_001243325.1	Q9H310-2
	RHBG	NM_001256395.2		c.736G>A	p.Gly246Arg	missense	Exon 7 of 11	NP_001243324.1	Q9H310-4

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RHBG	ENST00000537040.6	TSL:1 MANE Select	c.943G>A	p.Gly315Arg	missense	Exon 6 of 10	ENSP00000441197.2	Q9H310-1
	RHBG	ENST00000612897.4	TSL:1	n.*554G>A		non_coding_transcript_exon	Exon 7 of 11	ENSP00000477836.1	A0A087WTF7
	RHBG	ENST00000613460.4	TSL:1	n.*772G>A		non_coding_transcript_exon	Exon 7 of 11	ENSP00000483178.1	F6Q468

Frequencies

GnomAD3 genomes AF: 0.484 AC: 73532 AN: 151772 Hom.: 18168 Cov.: 31

Gnomad AFR AF: 0.540

Gnomad AMI AF: 0.550

Gnomad AMR AF: 0.549

Gnomad ASJ AF: 0.437

Gnomad EAS AF: 0.697

Gnomad SAS AF: 0.445

Gnomad FIN AF: 0.428

Gnomad MID AF: 0.465

Gnomad NFE AF: 0.434

Gnomad OTH AF: 0.476

GnomAD2 exomes AF: 0.481 AC: 117936 AN: 244952 AF XY: 0.470

Gnomad AFR exome AF: 0.547

Gnomad AMR exome AF: 0.610

Gnomad ASJ exome AF: 0.427

Gnomad EAS exome AF: 0.707

Gnomad FIN exome AF: 0.427

Gnomad NFE exome AF: 0.428

Gnomad OTH exome AF: 0.466

GnomAD4 exome AF: 0.446 AC: 650189 AN: 1457366 Hom.: 147704 Cov.: 50 AF XY: 0.445 AC XY: 322676 AN XY: 725250

African (AFR) AF: 0.545 AC: 18045 AN: 33086

American (AMR) AF: 0.604 AC: 25719 AN: 42608

Ashkenazi Jewish (ASJ) AF: 0.433 AC: 11210 AN: 25900

East Asian (EAS) AF: 0.698 AC: 27694 AN: 39680

South Asian (SAS) AF: 0.443 AC: 37998 AN: 85766

European-Finnish (FIN) AF: 0.429 AC: 22922 AN: 53386

Middle Eastern (MID) AF: 0.443 AC: 2551 AN: 5754

European-Non Finnish (NFE) AF: 0.429 AC: 476687 AN: 1110984

Other (OTH) AF: 0.455 AC: 27363 AN: 60202

GnomAD4 genome AF: 0.484 AC: 73562 AN: 151890 Hom.: 18171 Cov.: 31 AF XY: 0.483 AC XY: 35821 AN XY: 74212

African (AFR) AF: 0.540 AC: 22356 AN: 41426

American (AMR) AF: 0.549 AC: 8371 AN: 15254

Ashkenazi Jewish (ASJ) AF: 0.437 AC: 1518 AN: 3472

East Asian (EAS) AF: 0.698 AC: 3594 AN: 5152

South Asian (SAS) AF: 0.443 AC: 2133 AN: 4810

European-Finnish (FIN) AF: 0.428 AC: 4512 AN: 10534

Middle Eastern (MID) AF: 0.452 AC: 131 AN: 290

European-Non Finnish (NFE) AF: 0.434 AC: 29460 AN: 67942

Other (OTH) AF: 0.470 AC: 988 AN: 2102

Alfa AF: 0.451 Hom.: 46239

Bravo AF: 0.498

Asia WGS AF: 0.521 AC: 1813 AN: 3478

EpiCase AF: 0.425

EpiControl AF: 0.425

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.96
BayesDel_addAF	Benign	-0.080	T
BayesDel_noAF	Pathogenic	0.26
CADD	Pathogenic	32
DANN	Pathogenic	1.0
Eigen	Pathogenic	0.88
Eigen_PC	Pathogenic	0.78
FATHMM_MKL	Uncertain	0.96	D
MetaRNN	Benign	0.000030	T
MetaSVM	Uncertain	-0.25	T
PhyloP100		7.8
PrimateAI	Uncertain	0.67	T
REVEL	Uncertain	0.56
Sift4G	Pathogenic	0.0010	D
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
gMVP		0.98
Mutation Taster		=61/39	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.10		Details are displayed if max score is > 0.2

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs3748569;

hg19: chr1-156351699;

COSMIC: COSV54804391;

COSMIC: COSV54804391;