rs1077352

Variant names:

• chr16-53631425-G-A
• rs1077352
• NM_015272.5:c.3294+5014C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_015272.5(RPGRIP1L):​c.3294+5014C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.481 in 152,082 control chromosomes in the GnomAD database, including 21,581 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 0.48 (21581 hom., cov: 32)
• Consequence: RPGRIP1L NM_015272.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.29
• Publications: 10 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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.819 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.3294+5014C>T		intron	N/A	NP_056087.2	Q68CZ1-1
	RPGRIP1L	NM_001330538.2		c.3192+5014C>T		intron	N/A	NP_001317467.1	H3BV03
	RPGRIP1L	NM_001308334.3		c.3294+5014C>T		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.3294+5014C>T		intron	N/A	ENSP00000493946.1	Q68CZ1-1
	RPGRIP1L	ENST00000563746.5	TSL:1	c.3192+5014C>T		intron	N/A	ENSP00000457889.1	H3BV03
	RPGRIP1L	ENST00000621565.5	TSL:1	c.3294+5014C>T		intron	N/A	ENSP00000480698.1	A0A087WX34

Frequencies

GnomAD3 genomes AF: 0.481 AC: 73082 AN: 151964 Hom.: 21519 Cov.: 32

Gnomad AFR AF: 0.826

Gnomad AMI AF: 0.311

Gnomad AMR AF: 0.468

Gnomad ASJ AF: 0.379

Gnomad EAS AF: 0.613

Gnomad SAS AF: 0.417

Gnomad FIN AF: 0.200

Gnomad MID AF: 0.519

Gnomad NFE AF: 0.319

Gnomad OTH AF: 0.476

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

GnomAD4 genome AF: 0.481 AC: 73200 AN: 152082 Hom.: 21581 Cov.: 32 AF XY: 0.475 AC XY: 35309 AN XY: 74316

African (AFR) AF: 0.826 AC: 34284 AN: 41510

American (AMR) AF: 0.468 AC: 7149 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.379 AC: 1315 AN: 3466

East Asian (EAS) AF: 0.613 AC: 3170 AN: 5170

South Asian (SAS) AF: 0.417 AC: 2013 AN: 4824

European-Finnish (FIN) AF: 0.200 AC: 2113 AN: 10568

Middle Eastern (MID) AF: 0.514 AC: 151 AN: 294

European-Non Finnish (NFE) AF: 0.319 AC: 21704 AN: 67954

Other (OTH) AF: 0.482 AC: 1018 AN: 2112

Alfa AF: 0.355 Hom.: 6962

Bravo AF: 0.517

Asia WGS AF: 0.532 AC: 1853 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	5.9
DANN	Benign	0.53
PhyloP100		1.3
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: rs1077352; hg19: chr16-53665337;