rs3748569

Positions:

• chr1-156381908-G-A
• chr1-156381908-G-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. 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. Another nucleotide change resulting in the same amino acid substitution has been previously reported as Likely benign in UniProt.

• 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

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

Verdict is Benign. Variant got -12 ACMG points.

• 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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RHBG	NM_020407.5	c.943G>A	p.Gly315Arg	missense_variant	6/10	ENST00000537040.6	NP_065140.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RHBG	ENST00000537040.6	c.943G>A	p.Gly315Arg	missense_variant	6/10	1	NM_020407.5	ENSP00000441197.2

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

GnomAD3 exomes AF: 0.481 AC: 117936 AN: 244952 Hom.: 29438 AF XY: 0.470 AC XY: 62630 AN XY: 133274

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 SAS exome AF: 0.437

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

Gnomad4 AFR exome AF: 0.545

Gnomad4 AMR exome AF: 0.604

Gnomad4 ASJ exome AF: 0.433

Gnomad4 EAS exome AF: 0.698

Gnomad4 SAS exome AF: 0.443

Gnomad4 FIN exome AF: 0.429

Gnomad4 NFE exome AF: 0.429

Gnomad4 OTH exome AF: 0.455

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

Gnomad4 AFR AF: 0.540

Gnomad4 AMR AF: 0.549

Gnomad4 ASJ AF: 0.437

Gnomad4 EAS AF: 0.698

Gnomad4 SAS AF: 0.443

Gnomad4 FIN AF: 0.428

Gnomad4 NFE AF: 0.434

Gnomad4 OTH AF: 0.470

Alfa AF: 0.445 Hom.: 31631

Bravo AF: 0.498

TwinsUK AF: 0.407 AC: 1509

ALSPAC AF: 0.430 AC: 1657

ESP6500AA AF: 0.526 AC: 2175

ESP6500EA AF: 0.425 AC: 3575

ExAC AF: 0.479 AC: 57993

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 v4.3

Name	Calibrated prediction	Score	Prediction
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
PrimateAI	Uncertain	0.67	T
REVEL	Uncertain	0.56
Sift4G	Pathogenic	0.0010	D
Vest4		0.33
MutPred		0.91		Gain of methylation at G315 (P = 0.0123);
ClinPred		0.059	T
GERP RS		4.4
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
gMVP		0.98

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

Publications

LitVar

Other links and lift over

dbSNP: rs3748569; hg19: chr1-156351699; COSMIC: COSV54804391; COSMIC: COSV54804391;