rs1421092

Variant names:

• chr16-53700309-C-T
• rs1421092
• NM_015272.5:c.85+330G>A

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 8 publications found

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 Gene-Disease associations (from GenCC):

• ciliopathy

  Inheritance: AR Classification: DEFINITIVE, STRONG Submitted by: PanelApp Australia, ClinGen
• Meckel syndrome, type 5

  Inheritance: AR Classification: DEFINITIVE Submitted by: G2P
• Joubert syndrome 7

  Inheritance: AR Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae)
• COACH syndrome 1

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
• Joubert syndrome with renal defect

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
• Meckel syndrome

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_015272.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RPGRIP1L	NM_015272.5	MANE Select	c.85+330G>A		intron	N/A	NP_056087.2	Q68CZ1-1
	RPGRIP1L	NM_001330538.2		c.85+330G>A		intron	N/A	NP_001317467.1	H3BV03
	RPGRIP1L	NM_001308334.3		c.85+330G>A		intron	N/A	NP_001295263.1	A0A087WX34

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RPGRIP1L	ENST00000647211.2	MANE Select	c.85+330G>A		intron	N/A	ENSP00000493946.1	Q68CZ1-1
	RPGRIP1L	ENST00000563746.5	TSL:1	c.85+330G>A		intron	N/A	ENSP00000457889.1	H3BV03
	RPGRIP1L	ENST00000621565.5	TSL:1	c.85+330G>A		intron	N/A	ENSP00000480698.1	A0A087WX34

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

African (AFR) AF: 0.415 AC: 17206 AN: 41426

American (AMR) AF: 0.155 AC: 2364 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.204 AC: 707 AN: 3462

East Asian (EAS) AF: 0.440 AC: 2281 AN: 5182

South Asian (SAS) AF: 0.248 AC: 1197 AN: 4820

European-Finnish (FIN) AF: 0.0573 AC: 607 AN: 10588

Middle Eastern (MID) AF: 0.269 AC: 79 AN: 294

European-Non Finnish (NFE) AF: 0.123 AC: 8364 AN: 68004

Other (OTH) AF: 0.224 AC: 473 AN: 2110

Alfa AF: 0.149 Hom.: 624

Bravo AF: 0.236

Asia WGS AF: 0.352 AC: 1219 AN: 3472

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.43
CADD	Benign	14
DANN	Benign	0.59
PhyloP100		0.14
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs1421092; hg19: chr16-53734221;