1-156378087-C-A

Position:

• chr1-156378087-C-A

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_020407.5(RHBG):​c.472C>A​(p.Leu158Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 10/16 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 30)
• Consequence: RHBG NM_020407.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.564

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

Verdict is Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.3682059).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
RHBG	NM_020407.5	c.472C>A	p.Leu158Met	missense_variant	3/10	ENST00000537040.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RHBG	ENST00000537040.6	c.472C>A	p.Leu158Met	missense_variant	3/10	1	NM_020407.5	P1

Frequencies

GnomAD3 genomes Cov.: 30

GnomAD4 exome Cov.: 41

GnomAD4 genome Cov.: 30

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jun 18, 2021

The c.472C>A (p.L158M) alteration is located in exon 3 (coding exon 3) of the RHBG gene. This alteration results from a C to A substitution at nucleotide position 472, causing the leucine (L) at amino acid position 158 to be replaced by a methionine (M). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Benign	-0.13	T
BayesDel_noAF	Benign	-0.43
CADD	Benign	21
DANN	Uncertain	0.99
Eigen	Uncertain	0.32
Eigen_PC	Uncertain	0.28
FATHMM_MKL	Uncertain	0.78	D
M_CAP	Benign	0.010	T
MetaRNN	Benign	0.37	T
MetaSVM	Benign	-1.0	T
MutationTaster	Benign	0.99	D;D;D;D;D;D
PrimateAI	Benign	0.46	T
PROVEAN	Benign	-1.4	N
Sift	Benign	0.034	D
Sift4G	Benign	0.096	T
Vest4		0.31
MutPred		0.41		Loss of helix (P = 0.0626);
MVP		0.42
ClinPred		0.86	D
GERP RS		4.0
gMVP		0.45

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr1-156347878;