16-53622363-CAAAA-CAAAAA

Position:

• chr16-53622363-CAAAA-CAAAAA

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BA1

The NM_015272.5(RPGRIP1L):​c.3295-8dupT variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0661 in 429,872 control chromosomes in the GnomAD database, including 17 homozygotes. 1/1 splice prediction tools predict no significant impact on normal splicing. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.013 (17 hom., cov: 30)
  • Exomes 𝑓: 0.082 (0 hom.)
• Consequence: RPGRIP1L NM_015272.5 splice_region, intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.196

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]

RPGRIP1L (HGNC:):

ACMG classification

Verdict is Benign. Variant got -8 ACMG points.

• BA1: GnomAdExome4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0903 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RPGRIP1L	NM_015272.5	c.3295-8dupT		splice_region_variant, intron_variant		ENST00000647211.2	NP_056087.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RPGRIP1L	ENST00000647211.2	c.3295-8dupT		splice_region_variant, intron_variant			NM_015272.5	ENSP00000493946.1

Frequencies

GnomAD3 genomes AF: 0.0128 AC: 1264 AN: 98608 Hom.: 16 Cov.: 30

Gnomad AFR AF: 0.0353

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00799

Gnomad ASJ AF: 0.00122

Gnomad EAS AF: 0.00385

Gnomad SAS AF: 0.00325

Gnomad FIN AF: 0.00955

Gnomad MID AF: 0.0230

Gnomad NFE AF: 0.00302

Gnomad OTH AF: 0.0100

GnomAD3 exomes AF: 0.0827 AC: 2219 AN: 26824 Hom.: 0 AF XY: 0.0815 AC XY: 1135 AN XY: 13932

Gnomad AFR exome AF: 0.108

Gnomad AMR exome AF: 0.0925

Gnomad ASJ exome AF: 0.0995

Gnomad EAS exome AF: 0.0959

Gnomad SAS exome AF: 0.0796

Gnomad FIN exome AF: 0.0545

Gnomad NFE exome AF: 0.0668

Gnomad OTH exome AF: 0.0921

GnomAD4 exome AF: 0.0819 AC: 27140 AN: 331222 Hom.: 0 Cov.: 0 AF XY: 0.0816 AC XY: 14171 AN XY: 173740

Gnomad4 AFR exome AF: 0.0955

Gnomad4 AMR exome AF: 0.0840

Gnomad4 ASJ exome AF: 0.0823

Gnomad4 EAS exome AF: 0.0792

Gnomad4 SAS exome AF: 0.0869

Gnomad4 FIN exome AF: 0.0756

Gnomad4 NFE exome AF: 0.0813

Gnomad4 OTH exome AF: 0.0827

GnomAD4 genome AF: 0.0129 AC: 1274 AN: 98650 Hom.: 17 Cov.: 30 AF XY: 0.0130 AC XY: 607 AN XY: 46756

Gnomad4 AFR AF: 0.0354

Gnomad4 AMR AF: 0.00809

Gnomad4 ASJ AF: 0.00122

Gnomad4 EAS AF: 0.00386

Gnomad4 SAS AF: 0.00359

Gnomad4 FIN AF: 0.00955

Gnomad4 NFE AF: 0.00302

Gnomad4 OTH AF: 0.0114

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.060		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: rs113083177; hg19: chr16-53656275;