1-156378316-C-G

Variant names:

• chr1-156378316-C-G
• rs267598074
• NM_020407.5:c.590C>G

Variant summary

Our verdict is Uncertain significance. The variant received 4 ACMG points: 4P and 0B. PM2 PP3_Moderate

The NM_020407.5(RHBG):​c.590C>G​(p.Ser197Trp) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,820 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. S197L) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 31)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: RHBG NM_020407.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 7.73
• Publications: 0 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: Uncertain_significance. The variant received 4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.936

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.590C>G	p.Ser197Trp	missense	Exon 4 of 10	NP_065140.3	Q9H310-1
	RHBG	NM_001256396.2		c.500C>G	p.Ser167Trp	missense	Exon 5 of 11	NP_001243325.1	Q9H310-2
	RHBG	NM_001256395.2		c.383C>G	p.Ser128Trp	missense	Exon 5 of 11	NP_001243324.1	Q9H310-4

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RHBG	ENST00000537040.6	TSL:1 MANE Select	c.590C>G	p.Ser197Trp	missense	Exon 4 of 10	ENSP00000441197.2	Q9H310-1
	RHBG	ENST00000612897.4	TSL:1	n.*201C>G		non_coding_transcript_exon	Exon 5 of 11	ENSP00000477836.1	A0A087WTF7
	RHBG	ENST00000613460.4	TSL:1	n.*419C>G		non_coding_transcript_exon	Exon 5 of 11	ENSP00000483178.1	F6Q468

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461820 Hom.: 0 Cov.: 34 AF XY: 0.00000138 AC XY: 1 AN XY: 727216

African (AFR) AF: 0.00 AC: 0 AN: 33478

American (AMR) AF: 0.00 AC: 0 AN: 44714

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26124

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.0000116 AC: 1 AN: 86258

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53402

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1111990

Other (OTH) AF: 0.00 AC: 0 AN: 60386

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.75
BayesDel_addAF	Pathogenic	0.19	D
BayesDel_noAF	Uncertain	0.030
CADD	Uncertain	25
DANN	Uncertain	0.99
Eigen	Pathogenic	0.69
Eigen_PC	Uncertain	0.58
FATHMM_MKL	Uncertain	0.96	D
M_CAP	Benign	0.022	T
MetaRNN	Pathogenic	0.94	D
MetaSVM	Benign	-0.77	T
PhyloP100		7.7
PrimateAI	Uncertain	0.51	T
Sift4G	Pathogenic	0.0010	D
Vest4		0.82
MutPred		0.74		Loss of methylation at R198 (P = 0.0316)
MVP		0.54
ClinPred		0.99	D
GERP RS		4.8
gMVP		0.94
Mutation Taster		=23/77	disease causing

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: rs267598074; hg19: chr1-156348107;