16-67518392-A-G

Position:

• chr16-67518392-A-G

Variant summary

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

The XM_047434628.1(RIPOR1):​c.-245A>G variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.995 in 152,480 control chromosomes in the GnomAD database, including 75,536 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 1.0 (75469 hom., cov: 33)
  • Exomes 𝑓: 1.0 (67 hom.)
• Consequence: RIPOR1 XM_047434628.1 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.718

Genes affected

RIPOR1 (HGNC:25836): (RHO family interacting cell polarization regulator 1) Enables 14-3-3 protein binding activity. Involved in several processes, including establishment of Golgi localization; negative regulation of Rho guanyl-nucleotide exchange factor activity; and negative regulation of Rho protein signal transduction. Located in Golgi apparatus; cell leading edge; and membrane. [provided by Alliance of Genome Resources, Apr 2022]

ENSG00000276075 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.994 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RIPOR1	XM_047434628.1	c.-245A>G		5_prime_UTR_variant	1/22		XP_047290584.1
LOC100505942	NR_104656.1	n.430-7T>C		splice_region_variant, intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ENSG00000276075	ENST00000613438.3	n.110-7T>C		splice_region_variant, intron_variant		3
ENSG00000276075	ENST00000621378.3	n.453-7T>C		splice_region_variant, intron_variant		2
RIPOR1	ENST00000562116.1	c.-245A>G		upstream_gene_variant		3		ENSP00000455239.1

Frequencies

GnomAD3 genomes AF: 0.995 AC: 151471 AN: 152228 Hom.: 75406 Cov.: 33

Gnomad AFR AF: 0.999

Gnomad AMI AF: 1.00

Gnomad AMR AF: 1.00

Gnomad ASJ AF: 0.996

Gnomad EAS AF: 0.875

Gnomad SAS AF: 0.995

Gnomad FIN AF: 1.00

Gnomad MID AF: 0.997

Gnomad NFE AF: 1.00

Gnomad OTH AF: 0.996

GnomAD4 exome AF: 1.00 AC: 134 AN: 134 Hom.: 67 Cov.: 0 AF XY: 1.00 AC XY: 96 AN XY: 96

Gnomad4 AFR exome AF: 1.00

Gnomad4 AMR exome AF: 1.00

Gnomad4 ASJ exome AF: 1.00

Gnomad4 EAS exome AF: 1.00

Gnomad4 SAS exome AF: 1.00

Gnomad4 FIN exome AF: 1.00

Gnomad4 NFE exome AF: 1.00

Gnomad4 OTH exome AF: 1.00

GnomAD4 genome AF: 0.995 AC: 151593 AN: 152346 Hom.: 75469 Cov.: 33 AF XY: 0.994 AC XY: 74070 AN XY: 74494

Gnomad4 AFR AF: 0.999

Gnomad4 AMR AF: 1.00

Gnomad4 ASJ AF: 0.996

Gnomad4 EAS AF: 0.876

Gnomad4 SAS AF: 0.995

Gnomad4 FIN AF: 1.00

Gnomad4 NFE AF: 1.00

Gnomad4 OTH AF: 0.996

Alfa AF: 0.999 Hom.: 28199

Bravo AF: 0.994

Asia WGS AF: 0.958 AC: 3333 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	7.2
DANN	Benign	0.71

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs3743729; hg19: chr16-67552295;