1-156384556-T-TC

Variant names:

• chr1-156384556-T-TC
• rs11303415
• NM_020407.5:c.1271dupC

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BA1

The NM_020407.5(RHBG):​c.1271dupC​(p.Asp425ArgfsTer18) variant causes a frameshift change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.711 in 1,584,428 control chromosomes in the GnomAD database, including 405,729 homozygotes. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.64 (32780 hom., cov: 0)
  • Exomes 𝑓: 0.72 (372949 hom.)
• Consequence: RHBG NM_020407.5 frameshift
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.618
• Publications: 17 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 -8 ACMG points.

• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.734 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RHBG	NM_020407.5	MANE Select	c.1271dupC	p.Asp425ArgfsTer18	frameshift	Exon 9 of 10	NP_065140.3
	RHBG	NM_001256396.2		c.1181dupC	p.Asp395ArgfsTer18	frameshift	Exon 10 of 11	NP_001243325.1
	RHBG	NM_001256395.2		c.1064dupC	p.Asp356ArgfsTer18	frameshift	Exon 10 of 11	NP_001243324.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RHBG	ENST00000537040.6	TSL:1 MANE Select	c.1271dupC	p.Asp425ArgfsTer18	frameshift	Exon 9 of 10	ENSP00000441197.2
	RHBG	ENST00000612897.4	TSL:1	n.*882dupC		non_coding_transcript_exon	Exon 10 of 11	ENSP00000477836.1
	RHBG	ENST00000613460.4	TSL:1	n.*1100dupC		non_coding_transcript_exon	Exon 10 of 11	ENSP00000483178.1

Frequencies

GnomAD3 genomes AF: 0.642 AC: 97260 AN: 151554 Hom.: 32771 Cov.: 0

Gnomad AFR AF: 0.438

Gnomad AMI AF: 0.664

Gnomad AMR AF: 0.707

Gnomad ASJ AF: 0.733

Gnomad EAS AF: 0.443

Gnomad SAS AF: 0.665

Gnomad FIN AF: 0.760

Gnomad MID AF: 0.764

Gnomad NFE AF: 0.740

Gnomad OTH AF: 0.664

GnomAD2 exomes AF: 0.00134 AC: 305 AN: 228422 AF XY: 0.00136

Gnomad AFR exome AF: 0.00231

Gnomad AMR exome AF: 0.00191

Gnomad ASJ exome AF: 0.00848

Gnomad EAS exome AF: 0.0000575

Gnomad FIN exome AF: 0.0000492

Gnomad NFE exome AF: 0.000777

Gnomad OTH exome AF: 0.00353

GnomAD4 exome AF: 0.718 AC: 1029010 AN: 1432754 Hom.: 372949 Cov.: 46 AF XY: 0.717 AC XY: 509581 AN XY: 710592

African (AFR) AF: 0.421 AC: 13761 AN: 32724

American (AMR) AF: 0.672 AC: 28035 AN: 41744

Ashkenazi Jewish (ASJ) AF: 0.730 AC: 17806 AN: 24406

East Asian (EAS) AF: 0.466 AC: 18304 AN: 39278

South Asian (SAS) AF: 0.651 AC: 53957 AN: 82926

European-Finnish (FIN) AF: 0.746 AC: 39121 AN: 52428

Middle Eastern (MID) AF: 0.725 AC: 4076 AN: 5622

European-Non Finnish (NFE) AF: 0.743 AC: 812827 AN: 1094508

Other (OTH) AF: 0.696 AC: 41123 AN: 59118

GnomAD4 genome AF: 0.642 AC: 97311 AN: 151674 Hom.: 32780 Cov.: 0 AF XY: 0.644 AC XY: 47707 AN XY: 74078

African (AFR) AF: 0.437 AC: 18069 AN: 41302

American (AMR) AF: 0.708 AC: 10780 AN: 15232

Ashkenazi Jewish (ASJ) AF: 0.733 AC: 2542 AN: 3470

East Asian (EAS) AF: 0.443 AC: 2270 AN: 5128

South Asian (SAS) AF: 0.665 AC: 3187 AN: 4790

European-Finnish (FIN) AF: 0.760 AC: 8013 AN: 10546

Middle Eastern (MID) AF: 0.760 AC: 222 AN: 292

European-Non Finnish (NFE) AF: 0.740 AC: 50219 AN: 67898

Other (OTH) AF: 0.667 AC: 1405 AN: 2106

Alfa AF: 0.637 Hom.: 3475

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.62
Mutation Taster		=118/82	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		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: rs11303415; hg19: chr1-156354347; COSMIC: COSV54801170; COSMIC: COSV54801170;