rs190689604

Positions:

• chr16-53638442-T-C

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BS1 BS2

The NM_015272.5(RPGRIP1L):​c.2959-31A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00154 in 1,164,108 control chromosomes in the GnomAD database, including 5 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★). There are indicators that this mutation may affect the branch point..

• Frequency:
  • Genomes: 𝑓 0.0014 (0 hom., cov: 32)
  • Exomes 𝑓: 0.0016 (5 hom.)
• Consequence: RPGRIP1L NM_015272.5 intron
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 1.07

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 -14 ACMG points.

• BP4: This place is a probable branch point but likely benign (scored 2 / 10). Computational evidence support a benign effect (BayesDel_noAF=-0.81).
• BP6: Variant 16-53638442-T-C is Benign according to our data. Variant chr16-53638442-T-C is described in ClinVar as [Likely_benign]. Clinvar id is 260602.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population amr. gnomad4 allele frequency = 0.00142 (216/152126) while in subpopulation AMR AF= 0.00281 (43/15278). AF 95% confidence interval is 0.00215. There are 0 homozygotes in gnomad4. There are 99 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High Homozygotes in GnomAdExome4 at 5 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
RPGRIP1L	NM_015272.5	c.2959-31A>G		intron_variant		ENST00000647211.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RPGRIP1L	ENST00000647211.2	c.2959-31A>G		intron_variant			NM_015272.5

Frequencies

GnomAD3 genomes AF: 0.00142 AC: 216 AN: 152010 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.000434

Gnomad AMI AF: 0.00110

Gnomad AMR AF: 0.00282

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.0000943

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00221

Gnomad OTH AF: 0.00144

GnomAD3 exomes AF: 0.00118 AC: 288 AN: 243992 Hom.: 0 AF XY: 0.00116 AC XY: 153 AN XY: 132190

Gnomad AFR exome AF: 0.000769

Gnomad AMR exome AF: 0.00186

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.0000480

Gnomad NFE exome AF: 0.00184

Gnomad OTH exome AF: 0.00168

GnomAD4 exome AF: 0.00156 AC: 1576 AN: 1011982 Hom.: 5 Cov.: 14 AF XY: 0.00155 AC XY: 808 AN XY: 522918

Gnomad4 AFR exome AF: 0.000363

Gnomad4 AMR exome AF: 0.00162

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.000192

Gnomad4 NFE exome AF: 0.00201

Gnomad4 OTH exome AF: 0.00164

GnomAD4 genome AF: 0.00142 AC: 216 AN: 152126 Hom.: 0 Cov.: 32 AF XY: 0.00133 AC XY: 99 AN XY: 74368

Gnomad4 AFR AF: 0.000433

Gnomad4 AMR AF: 0.00281

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.0000943

Gnomad4 NFE AF: 0.00221

Gnomad4 OTH AF: 0.00142

Alfa AF: 0.00143 Hom.: 0

Bravo AF: 0.00137

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Benign:1

Likely benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	13
DANN	Benign	0.67
BranchPoint Hunter		2.0

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: rs190689604; hg19: chr16-53672354;