chr1-156384556-T-TCCC

Variant names:

• chr1-156384556-T-TCCC
• rs11303415
• NM_020407.5:c.1269_1271dupCCC

Variant summary

Our verdict is Uncertain significance. The variant received 3 ACMG points: 3P and 0B. PM2 PM4_Supporting

The NM_020407.5(RHBG):​c.1269_1271dupCCC​(p.Pro424dup) variant causes a disruptive inframe insertion change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000014 in 1,433,128 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 0)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: RHBG NM_020407.5 disruptive_inframe_insertion
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.618
• 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 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PM4: Nonframeshift variant in NON repetitive region in NM_020407.5. Strenght limited to Supporting due to length of the change: 1aa.

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.1269_1271dupCCC	p.Pro424dup	disruptive_inframe_insertion	Exon 9 of 10	NP_065140.3
	RHBG	NM_001256396.2		c.1179_1181dupCCC	p.Pro394dup	disruptive_inframe_insertion	Exon 10 of 11	NP_001243325.1
	RHBG	NM_001256395.2		c.1062_1064dupCCC	p.Pro355dup	disruptive_inframe_insertion	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.1269_1271dupCCC	p.Pro424dup	disruptive_inframe_insertion	Exon 9 of 10	ENSP00000441197.2
	RHBG	ENST00000612897.4	TSL:1	n.*880_*882dupCCC		non_coding_transcript_exon	Exon 10 of 11	ENSP00000477836.1
	RHBG	ENST00000613460.4	TSL:1	n.*1098_*1100dupCCC		non_coding_transcript_exon	Exon 10 of 11	ENSP00000483178.1

Frequencies

GnomAD3 genomes Cov.: 0

GnomAD4 exome AF: 0.00000140 AC: 2 AN: 1433128 Hom.: 0 Cov.: 46 AF XY: 0.00000141 AC XY: 1 AN XY: 710794

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00 AC: 0 AN: 32760

American (AMR) AF: 0.0000479 AC: 2 AN: 41790

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 24424

East Asian (EAS) AF: 0.00 AC: 0 AN: 39286

South Asian (SAS) AF: 0.00 AC: 0 AN: 82972

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52446

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5622

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1094692

Other (OTH) AF: 0.00 AC: 0 AN: 59136

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0.00666416), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Cov.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.62

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs11303415; hg19: chr1-156354347;