16-53703648-G-A

Position:

• chr16-53703648-G-A

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_015272.5(RPGRIP1L):​c.-8+155C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0421 in 212,652 control chromosomes in the GnomAD database, including 314 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.047 (268 hom., cov: 32)
  • Exomes 𝑓: 0.030 (46 hom.)
• Consequence: RPGRIP1L NM_015272.5 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.565

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]

FTO (HGNC:24678): (FTO alpha-ketoglutarate dependent dioxygenase) This gene is a nuclear protein of the AlkB related non-haem iron and 2-oxoglutarate-dependent oxygenase superfamily but the exact physiological function of this gene is not known. Other non-heme iron enzymes function to reverse alkylated DNA and RNA damage by oxidative demethylation. Studies in mice and humans indicate a role in nervous and cardiovascular systems and a strong association with body mass index, obesity risk, and type 2 diabetes. [provided by RefSeq, Jul 2011]

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.71).
• BP6: Variant 16-53703648-G-A is Benign according to our data. Variant chr16-53703648-G-A is described in ClinVar as [Benign]. Clinvar id is 1174271.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0957 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RPGRIP1L	NM_015272.5	c.-8+155C>T		intron_variant		ENST00000647211.2	NP_056087.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RPGRIP1L	ENST00000647211.2	c.-8+155C>T		intron_variant			NM_015272.5	ENSP00000493946

Frequencies

GnomAD3 genomes AF: 0.0470 AC: 7143 AN: 152114 Hom.: 266 Cov.: 32

Gnomad AFR AF: 0.0984

Gnomad AMI AF: 0.0208

Gnomad AMR AF: 0.0272

Gnomad ASJ AF: 0.0793

Gnomad EAS AF: 0.000386

Gnomad SAS AF: 0.0652

Gnomad FIN AF: 0.00697

Gnomad MID AF: 0.0696

Gnomad NFE AF: 0.0270

Gnomad OTH AF: 0.0537

GnomAD4 exome AF: 0.0298 AC: 1801 AN: 60420 Hom.: 46 Cov.: 0 AF XY: 0.0307 AC XY: 970 AN XY: 31596

Gnomad4 AFR exome AF: 0.0906

Gnomad4 AMR exome AF: 0.0264

Gnomad4 ASJ exome AF: 0.0616

Gnomad4 EAS exome AF: 0.000243

Gnomad4 SAS exome AF: 0.0583

Gnomad4 FIN exome AF: 0.0119

Gnomad4 NFE exome AF: 0.0220

Gnomad4 OTH exome AF: 0.0297

GnomAD4 genome AF: 0.0470 AC: 7151 AN: 152232 Hom.: 268 Cov.: 32 AF XY: 0.0450 AC XY: 3349 AN XY: 74416

Gnomad4 AFR AF: 0.0983

Gnomad4 AMR AF: 0.0271

Gnomad4 ASJ AF: 0.0793

Gnomad4 EAS AF: 0.000387

Gnomad4 SAS AF: 0.0661

Gnomad4 FIN AF: 0.00697

Gnomad4 NFE AF: 0.0270

Gnomad4 OTH AF: 0.0532

Alfa AF: 0.0153 Hom.: 9

Bravo AF: 0.0493

Asia WGS AF: 0.0360 AC: 125 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Feb 24, 2021	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.71
CADD	Benign	1.1
DANN	Benign	0.85

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		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: rs62048369; hg19: chr16-53737560;