rs1421092

chr16-53700309-C-T

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_Moderate BA1

The NM_015272.5(RPGRIP1L):c.85+330G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.22 in 152,094 control chromosomes in the GnomAD database, including 5,175 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 0.22 (5175 hom., cov: 32)
• Consequence: RPGRIP1L NM_015272.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.135

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 -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.43).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.425 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
RPGRIP1L	NM_015272.5	c.85+330G>A		intron_variant		ENST00000647211.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RPGRIP1L	ENST00000647211.2	c.85+330G>A		intron_variant			NM_015272.5

Frequencies

GnomAD3 genomes AF: 0.219 AC: 33321 AN: 151976 Hom.: 5135 Cov.: 32

Gnomad AFR AF: 0.414

Gnomad AMI AF: 0.151

Gnomad AMR AF: 0.154

Gnomad ASJ AF: 0.204

Gnomad EAS AF: 0.441

Gnomad SAS AF: 0.249

Gnomad FIN AF: 0.0573

Gnomad MID AF: 0.275

Gnomad NFE AF: 0.123

Gnomad OTH AF: 0.215

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

GnomAD4 genome AF: 0.220 AC: 33415 AN: 152094 Hom.: 5175 Cov.: 32 AF XY: 0.217 AC XY: 16115 AN XY: 74330

Gnomad4 AFR AF: 0.415

Gnomad4 AMR AF: 0.155

Gnomad4 ASJ AF: 0.204

Gnomad4 EAS AF: 0.440

Gnomad4 SAS AF: 0.248

Gnomad4 FIN AF: 0.0573

Gnomad4 NFE AF: 0.123

Gnomad4 OTH AF: 0.224

Alfa AF: 0.177 Hom.: 497

Bravo AF: 0.236

Asia WGS AF: 0.352 AC: 1219 AN: 3472

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.43
Cadd	Benign	14
Dann	Benign	0.59

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: rs1421092; hg19: chr16-53734221;