rs147708513

Variant names:

• chr16-53622182-G-A
• rs147708513
• NM_015272.5:c.3432+37C>T

Your query was ambiguous. Multiple possible variants found:

• chr16-53622182-G-A
• chr16-53622182-G-C
• chr16-53622182-G-T

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. 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
• Publications: 0 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):

• 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=-0.92).
• 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 VariationId 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 the male GnomAd4 subpopulation. Median coverage is 29. This position passed quality control check.

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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RPGRIP1L	NM_015272.5	MANE Select	c.3432+37C>T		intron	N/A	NP_056087.2
	RPGRIP1L	NM_001330538.2		c.3330+37C>T		intron	N/A	NP_001317467.1
	RPGRIP1L	NM_001308334.3		c.3295-2974C>T		intron	N/A	NP_001295263.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RPGRIP1L	ENST00000647211.2	MANE Select	c.3432+37C>T		intron	N/A	ENSP00000493946.1
	RPGRIP1L	ENST00000563746.5	TSL:1	c.3330+37C>T		intron	N/A	ENSP00000457889.1
	RPGRIP1L	ENST00000621565.5	TSL:1	c.3295-2974C>T		intron	N/A	ENSP00000480698.1

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

GnomAD2 exomes AF: 0.00115 AC: 88 AN: 76666 AF XY: 0.000881

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 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

African (AFR) AF: 0.00425 AC: 54 AN: 12692

American (AMR) AF: 0.00175 AC: 46 AN: 26354

Ashkenazi Jewish (ASJ) AF: 0.00316 AC: 50 AN: 15826

East Asian (EAS) AF: 0.00 AC: 0 AN: 29204

South Asian (SAS) AF: 0.0000206 AC: 1 AN: 48546

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 30198

Middle Eastern (MID) AF: 0.00817 AC: 17 AN: 2082

European-Non Finnish (NFE) AF: 0.000331 AC: 91 AN: 275112

Other (OTH) AF: 0.00120 AC: 32 AN: 26614

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

African (AFR) AF: 0.00301 AC: 124 AN: 41180

American (AMR) AF: 0.00125 AC: 19 AN: 15180

Ashkenazi Jewish (ASJ) AF: 0.00288 AC: 10 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5088

South Asian (SAS) AF: 0.000209 AC: 1 AN: 4780

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10442

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 290

European-Non Finnish (NFE) AF: 0.000251 AC: 17 AN: 67828

Other (OTH) AF: 0.00190 AC: 4 AN: 2100

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

PreventionGenetics, part of Exact Sciences

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	3.2
DANN	Benign	0.58
PhyloP100		0.25

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

Other links and lift over

dbSNP: rs147708513; hg19: chr16-53656094;