15-89471714-T-G

Position:

• chr15-89471714-T-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_016321.3(RHCG):​c.*166A>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.594 in 152,756 control chromosomes in the GnomAD database, including 28,424 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 0.59 (28338 hom., cov: 32)
  • Exomes 𝑓: 0.53 (86 hom.)
• Consequence: RHCG NM_016321.3 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0880

Genes affected

RHCG (HGNC:18140): (Rh family C glycoprotein) Enables ammonium transmembrane transporter activity; ankyrin binding activity; and identical protein binding activity. Involved in ammonium transmembrane transport; cellular ion homeostasis; and transepithelial ammonium transport. Located in apical plasma membrane and basolateral plasma membrane. Is integral component of plasma membrane. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.799 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
RHCG	NM_016321.3	c.*166A>C		3_prime_UTR_variant	11/11	ENST00000268122.9
RHCG	NM_001321041.2	c.*155A>C		3_prime_UTR_variant	11/11
RHCG	XM_047432651.1	c.*239A>C		3_prime_UTR_variant	11/11
RHCG	NR_110261.2	n.1558A>C		non_coding_transcript_exon_variant	11/11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RHCG	ENST00000268122.9	c.*166A>C		3_prime_UTR_variant	11/11	1	NM_016321.3	P1

Frequencies

GnomAD3 genomes AF: 0.595 AC: 90355 AN: 151950 Hom.: 28297 Cov.: 32

Gnomad AFR AF: 0.806

Gnomad AMI AF: 0.696

Gnomad AMR AF: 0.590

Gnomad ASJ AF: 0.524

Gnomad EAS AF: 0.377

Gnomad SAS AF: 0.396

Gnomad FIN AF: 0.490

Gnomad MID AF: 0.525

Gnomad NFE AF: 0.517

Gnomad OTH AF: 0.574

GnomAD4 exome AF: 0.526 AC: 361 AN: 686 Hom.: 86 Cov.: 0 AF XY: 0.505 AC XY: 222 AN XY: 440

Gnomad4 AFR exome AF: 0.800

Gnomad4 AMR exome AF: 0.500

Gnomad4 ASJ exome AF: 0.333

Gnomad4 EAS exome AF: 0.500

Gnomad4 FIN exome AF: 0.534

Gnomad4 NFE exome AF: 0.506

Gnomad4 OTH exome AF: 0.438

GnomAD4 genome AF: 0.595 AC: 90450 AN: 152070 Hom.: 28338 Cov.: 32 AF XY: 0.589 AC XY: 43778 AN XY: 74320

Gnomad4 AFR AF: 0.806

Gnomad4 AMR AF: 0.590

Gnomad4 ASJ AF: 0.524

Gnomad4 EAS AF: 0.377

Gnomad4 SAS AF: 0.396

Gnomad4 FIN AF: 0.490

Gnomad4 NFE AF: 0.517

Gnomad4 OTH AF: 0.574

Alfa AF: 0.528 Hom.: 19275

Bravo AF: 0.614

Asia WGS AF: 0.435 AC: 1512 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	3.6
DANN	Benign	0.79

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

LitVar

Other links and lift over

dbSNP: rs2072693; hg19: chr15-90014945; COSMIC: COSV51516115; COSMIC: COSV51516115;