Genetic Variant NM_020407.5:c.428T>A (chr1-156378043-T-A) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

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

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 7.89

Publications

20 publications found

Variant links:

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 links:

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ACMG classification

Classification was made for transcript

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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RHBG	NM_020407.5 link	c.428T>A	p.Val143Asp	missense_variant	Exon 3 of 10	ENST00000537040.6	NP_065140.3	Q9H310-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RHBG	ENST00000537040.6 link	c.428T>A	p.Val143Asp	missense_variant	Exon 3 of 10	1	NM_020407.5	ENSP00000441197.2		Q9H310-1

Frequencies

GnomAD3 genomes

AF:

0.235

AC:

35631

AN:

151768

Hom.:

4365

Cov.:

show subpopulations

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

show subpopulations

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.:

AF XY:

0.241

AC XY:

171991

AN XY:

712780

show subpopulations

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

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.482

Heterozygous variant carriers

14024

28048

42073

56097

70121

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

8904

17808

26712

35616

44520

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.235

AC:

35635

AN:

151886

Hom.:

4363

Cov.:

AF XY:

0.238

AC XY:

17665

AN XY:

74184

show subpopulations

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:

AN:

294

European-Non Finnish (NFE)

AF:

0.235

AC:

15968

AN:

67918

Other (OTH)

AF:

0.244

AC:

516

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

1364

2729

4093

5458

6822

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

384

768

1152

1536

1920

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

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

BayesDel_noAF

Uncertain

-0.080

CADD

Pathogenic

(source)

DANN

Uncertain

0.98

Eigen

Uncertain

0.53

Eigen_PC

Uncertain

0.43

FATHMM_MKL

Uncertain

0.92

MetaRNN

Benign

0.0028

MetaSVM

Benign

-0.45

PhyloP100

7.9

PrimateAI

Benign

0.39

Sift4G

Pathogenic

0.0

Vest4

0.30

ClinPred

0.045

GERP RS

5.0

gMVP

0.96

Mutation Taster

=97/3

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over