rs8055834

chr16-53686983-C-Achr16-53686983-C-T

Variant summary

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

The NM_015272.5(RPGRIP1L):c.633-407G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0361 in 152,188 control chromosomes in the GnomAD database, including 142 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 0.036 (142 hom., cov: 32)
• Consequence: RPGRIP1L NM_015272.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.113

Genes affected

RPGRIP1L (HGNC:29168): (RPGRIP1 like) The protein encoded by this gene can localize to the basal body-centrosome complex or to primary cilia and centrosomes in ciliated cells. The encoded protein has been found to interact with nephrocystin-4. Defects in this gene are a cause of Joubert syndrome type 7 (JBTS7) and Meckel syndrome type 5 (MKS5). [provided by RefSeq, Jun 2016]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.79).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.082 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
RPGRIP1L	NM_015272.5	c.633-407G>T		intron_variant		ENST00000647211.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RPGRIP1L	ENST00000647211.2	c.633-407G>T		intron_variant			NM_015272.5

Frequencies

GnomAD3 genomes AF: 0.0360 AC: 5481 AN: 152070 Hom.: 142 Cov.: 32

Gnomad AFR AF: 0.0537

Gnomad AMI AF: 0.0208

Gnomad AMR AF: 0.0179

Gnomad ASJ AF: 0.00922

Gnomad EAS AF: 0.0887

Gnomad SAS AF: 0.0443

Gnomad FIN AF: 0.0120

Gnomad MID AF: 0.00949

Gnomad NFE AF: 0.0305

Gnomad OTH AF: 0.0273

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.0361 AC: 5490 AN: 152188 Hom.: 142 Cov.: 32 AF XY: 0.0350 AC XY: 2607 AN XY: 74416

Gnomad4 AFR AF: 0.0537

Gnomad4 AMR AF: 0.0179

Gnomad4 ASJ AF: 0.00922

Gnomad4 EAS AF: 0.0887

Gnomad4 SAS AF: 0.0448

Gnomad4 FIN AF: 0.0120

Gnomad4 NFE AF: 0.0305

Gnomad4 OTH AF: 0.0270

Alfa AF: 0.0323 Hom.: 26

Bravo AF: 0.0367

Asia WGS AF: 0.0530 AC: 185 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
Cadd	Benign	0.58
Dann	Benign	0.77

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

Publications

LitVar

Other links and lift over

dbSNP: rs8055834; hg19: chr16-53720895;