chr1-156378043-T-A

Position:

• chr1-156378043-T-A

Variant summary

Our verdict is Benign. Variant got -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. Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

• 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

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]

RHBG (HGNC:):

ACMG classification

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RHBG	NM_020407.5	c.428T>A	p.Val143Asp	missense_variant	3/10	ENST00000537040.6	NP_065140.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RHBG	ENST00000537040.6	c.428T>A	p.Val143Asp	missense_variant	3/10	1	NM_020407.5	ENSP00000441197.2

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

GnomAD3 exomes AF: 0.260 AC: 59870 AN: 230696 Hom.: 8052 AF XY: 0.257 AC XY: 31905 AN XY: 124220

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 SAS exome AF: 0.264

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

Gnomad4 AFR exome AF: 0.165

Gnomad4 AMR exome AF: 0.337

Gnomad4 ASJ exome AF: 0.292

Gnomad4 EAS exome AF: 0.357

Gnomad4 SAS exome AF: 0.266

Gnomad4 FIN exome AF: 0.256

Gnomad4 NFE exome AF: 0.230

Gnomad4 OTH exome AF: 0.244

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

Gnomad4 AFR AF: 0.170

Gnomad4 AMR AF: 0.322

Gnomad4 ASJ AF: 0.295

Gnomad4 EAS AF: 0.337

Gnomad4 SAS AF: 0.271

Gnomad4 FIN AF: 0.265

Gnomad4 NFE AF: 0.235

Gnomad4 OTH AF: 0.244

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 v4.3

Name	Calibrated prediction	Score	Prediction
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
PrimateAI	Benign	0.39	T
Sift4G	Pathogenic	0.0	D
Vest4		0.30
ClinPred		0.045	T
GERP RS		5.0
gMVP		0.96

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

Publications

LitVar

Other links and lift over

dbSNP: rs11586833; hg19: chr1-156347834; COSMIC: COSV54801576; COSMIC: COSV54801576;