rs11586833

Variant names:

• chr1-156378043-T-A
• rs11586833
• NM_020407.5:c.428T>A

Your query was ambiguous. Multiple possible variants found:

• chr1-156378043-T-A
• chr1-156378043-T-C

Variant summary

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

The NM_020407.5(RHBG):​c.428T>A​(p.Val143Asp) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.24 in 1,589,784 control chromosomes in the GnomAD database, including 46,876 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 0.23 (4363 hom., cov: 31)
  • Exomes 𝑓: 0.24 (42513 hom.)
• Consequence: RHBG NM_020407.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 7.89
• Publications: 20 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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.002765745).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.324 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.428T>A	p.Val143Asp	missense	Exon 3 of 10	NP_065140.3
	RHBG	NM_001256396.2		c.338T>A	p.Val113Asp	missense	Exon 4 of 11	NP_001243325.1
	RHBG	NM_001256395.2		c.221T>A	p.Val74Asp	missense	Exon 4 of 11	NP_001243324.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RHBG	ENST00000537040.6	TSL:1 MANE Select	c.428T>A	p.Val143Asp	missense	Exon 3 of 10	ENSP00000441197.2
	RHBG	ENST00000612897.4	TSL:1	n.*39T>A		non_coding_transcript_exon	Exon 4 of 11	ENSP00000477836.1
	RHBG	ENST00000613460.4	TSL:1	n.*257T>A		non_coding_transcript_exon	Exon 4 of 11	ENSP00000483178.1

Frequencies

GnomAD3 genomes AF: 0.235 AC: 35631 AN: 151768 Hom.: 4365 Cov.: 31

Gnomad AFR AF: 0.171

Gnomad AMI AF: 0.248

Gnomad AMR AF: 0.321

Gnomad ASJ AF: 0.295

Gnomad EAS AF: 0.337

Gnomad SAS AF: 0.272

Gnomad FIN AF: 0.265

Gnomad MID AF: 0.335

Gnomad NFE AF: 0.235

Gnomad OTH AF: 0.246

GnomAD2 exomes AF: 0.260 AC: 59870 AN: 230696 AF XY: 0.257

Gnomad AFR exome AF: 0.168

Gnomad AMR exome AF: 0.342

Gnomad ASJ exome AF: 0.287

Gnomad EAS exome AF: 0.323

Gnomad FIN exome AF: 0.261

Gnomad NFE exome AF: 0.233

Gnomad OTH exome AF: 0.260

GnomAD4 exome AF: 0.240 AC: 345450 AN: 1437898 Hom.: 42513 Cov.: 42 AF XY: 0.241 AC XY: 171991 AN XY: 712780

African (AFR) AF: 0.165 AC: 5451 AN: 32998

American (AMR) AF: 0.337 AC: 14173 AN: 42108

Ashkenazi Jewish (ASJ) AF: 0.292 AC: 7097 AN: 24328

East Asian (EAS) AF: 0.357 AC: 14091 AN: 39482

South Asian (SAS) AF: 0.266 AC: 21869 AN: 82082

European-Finnish (FIN) AF: 0.256 AC: 13418 AN: 52462

Middle Eastern (MID) AF: 0.306 AC: 1728 AN: 5656

European-Non Finnish (NFE) AF: 0.230 AC: 253103 AN: 1099388

Other (OTH) AF: 0.244 AC: 14520 AN: 59394

GnomAD4 genome AF: 0.235 AC: 35635 AN: 151886 Hom.: 4363 Cov.: 31 AF XY: 0.238 AC XY: 17665 AN XY: 74184

African (AFR) AF: 0.170 AC: 7060 AN: 41422

American (AMR) AF: 0.322 AC: 4910 AN: 15262

Ashkenazi Jewish (ASJ) AF: 0.295 AC: 1024 AN: 3472

East Asian (EAS) AF: 0.337 AC: 1732 AN: 5134

South Asian (SAS) AF: 0.271 AC: 1303 AN: 4800

European-Finnish (FIN) AF: 0.265 AC: 2802 AN: 10560

Middle Eastern (MID) AF: 0.320 AC: 94 AN: 294

European-Non Finnish (NFE) AF: 0.235 AC: 15968 AN: 67918

Other (OTH) AF: 0.244 AC: 516 AN: 2114

Alfa AF: 0.242 Hom.: 2948

Bravo AF: 0.236

TwinsUK AF: 0.213 AC: 791

ALSPAC AF: 0.225 AC: 867

ESP6500AA AF: 0.160 AC: 670

ESP6500EA AF: 0.233 AC: 1969

ExAC AF: 0.252 AC: 30501

Asia WGS AF: 0.283 AC: 986 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.85
BayesDel_addAF	Benign	-0.31	T
BayesDel_noAF	Uncertain	-0.080
CADD	Pathogenic	26
DANN	Uncertain	0.98
Eigen	Uncertain	0.53
Eigen_PC	Uncertain	0.43
FATHMM_MKL	Uncertain	0.92	D
MetaRNN	Benign	0.0028	T
MetaSVM	Benign	-0.45	T
PhyloP100		7.9
PrimateAI	Benign	0.39	T
Sift4G	Pathogenic	0.0	D
Vest4		0.30
ClinPred		0.045	T
GERP RS		5.0
gMVP		0.96
Mutation Taster		=97/3	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: rs11586833; hg19: chr1-156347834; COSMIC: COSV54801576; COSMIC: COSV54801576;