rs147708513

Positions:

• chr16-53622182-G-A

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 2P and 10B. PM2 BP4_Strong BP6_Moderate BS1

The NM_015272.5(RPGRIP1L):​c.3432+37C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000754 in 617,890 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0012 (0 hom., cov: 29)
  • Exomes 𝑓: 0.00062 (0 hom.)
• Consequence: RPGRIP1L NM_015272.5 intron
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.252

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 -8 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BP6: Variant 16-53622182-G-A is Benign according to our data. Variant chr16-53622182-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 260605.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00116 (175/151262) while in subpopulation AFR AF= 0.00301 (124/41180). AF 95% confidence interval is 0.00258. There are 0 homozygotes in gnomad4. There are 77 alleles in male gnomad4 subpopulation. Median coverage is 29. This position pass quality control queck.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
RPGRIP1L	NM_015272.5	c.3432+37C>T		intron_variant		ENST00000647211.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RPGRIP1L	ENST00000647211.2	c.3432+37C>T		intron_variant			NM_015272.5

Frequencies

GnomAD3 genomes AF: 0.00114 AC: 173 AN: 151144 Hom.: 0 Cov.: 29

Gnomad AFR AF: 0.00297

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00125

Gnomad ASJ AF: 0.00288

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000209

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000251

Gnomad OTH AF: 0.00192

GnomAD3 exomes AF: 0.00115 AC: 88 AN: 76666 Hom.: 0 AF XY: 0.000881 AC XY: 36 AN XY: 40874

Gnomad AFR exome AF: 0.00550

Gnomad AMR exome AF: 0.00200

Gnomad ASJ exome AF: 0.00467

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000327

Gnomad OTH exome AF: 0.000816

GnomAD4 exome AF: 0.000624 AC: 291 AN: 466628 Hom.: 0 Cov.: 0 AF XY: 0.000550 AC XY: 137 AN XY: 249178

Gnomad4 AFR exome AF: 0.00425

Gnomad4 AMR exome AF: 0.00175

Gnomad4 ASJ exome AF: 0.00316

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000206

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.000331

Gnomad4 OTH exome AF: 0.00120

GnomAD4 genome AF: 0.00116 AC: 175 AN: 151262 Hom.: 0 Cov.: 29 AF XY: 0.00104 AC XY: 77 AN XY: 73858

Gnomad4 AFR AF: 0.00301

Gnomad4 AMR AF: 0.00125

Gnomad4 ASJ AF: 0.00288

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000209

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000251

Gnomad4 OTH AF: 0.00190

Alfa AF: 0.00132 Hom.: 1

Bravo AF: 0.00150

Asia WGS AF: 0.00144 AC: 5 AN: 3478

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

-

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	3.2
DANN	Benign	0.58

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs147708513; hg19: chr16-53656094;