8-10606565-A-C

Position:

• chr8-10606565-A-C

Variant summary

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

The ENST00000382483.4(RP1L1):​c.*330T>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.143 in 326,108 control chromosomes in the GnomAD database, including 4,178 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.15 (2025 hom., cov: 34)
  • Exomes 𝑓: 0.14 (2153 hom.)
• Consequence: RP1L1 ENST00000382483.4 3_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.626

Genes affected

RP1L1 (HGNC:15946): (RP1 like 1) This gene encodes a member of the doublecortin family. The protein encoded by this gene contains two N-terminal doublecortin domains, which bind microtubules and regulate microtubule polymerization, and two C-terminal large repetitive regions, both of which contain a high percentage of glutamine and glutamic acid residues. This protein is a retinal-specific protein. Its exact length varies among individuals due to the presence of a 16aa repeat in the first C-terminal repetitive region. The 16aa repeat is encoded by the highly polymorphic 48-bp repeat, and 1-6 copies of the 16aa repeat have been identified in normal individuals. The current reference sequence shown here has a single copy of the 16aa repeat. This protein and the RP1 protein, another retinal-specific protein, play essential and synergistic roles in affecting photosensitivity and outer segment morphogenesis of rod photoreceptors. Mutations in this gene cause occult macular dystrophy (OMD). [provided by RefSeq, Sep 2010]

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BP6: Variant 8-10606565-A-C is Benign according to our data. Variant chr8-10606565-A-C is described in ClinVar as [Benign]. Clinvar id is 361191.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.396 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RP1L1	NM_178857.6	c.*330T>G		3_prime_UTR_variant	4/4	ENST00000382483.4	NP_849188.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RP1L1	ENST00000382483.4	c.*330T>G		3_prime_UTR_variant	4/4	1	NM_178857.6	ENSP00000371923	P1

Frequencies

GnomAD3 genomes AF: 0.150 AC: 22853 AN: 152088 Hom.: 2015 Cov.: 34

Gnomad AFR AF: 0.173

Gnomad AMI AF: 0.130

Gnomad AMR AF: 0.171

Gnomad ASJ AF: 0.121

Gnomad EAS AF: 0.411

Gnomad SAS AF: 0.114

Gnomad FIN AF: 0.0660

Gnomad MID AF: 0.149

Gnomad NFE AF: 0.130

Gnomad OTH AF: 0.148

GnomAD4 exome AF: 0.137 AC: 23797 AN: 173902 Hom.: 2153 Cov.: 2 AF XY: 0.136 AC XY: 12385 AN XY: 91378

Gnomad4 AFR exome AF: 0.174

Gnomad4 AMR exome AF: 0.148

Gnomad4 ASJ exome AF: 0.106

Gnomad4 EAS exome AF: 0.390

Gnomad4 SAS exome AF: 0.114

Gnomad4 FIN exome AF: 0.0690

Gnomad4 NFE exome AF: 0.125

Gnomad4 OTH exome AF: 0.134

GnomAD4 genome AF: 0.150 AC: 22894 AN: 152206 Hom.: 2025 Cov.: 34 AF XY: 0.148 AC XY: 10991 AN XY: 74432

Gnomad4 AFR AF: 0.173

Gnomad4 AMR AF: 0.171

Gnomad4 ASJ AF: 0.121

Gnomad4 EAS AF: 0.411

Gnomad4 SAS AF: 0.114

Gnomad4 FIN AF: 0.0660

Gnomad4 NFE AF: 0.130

Gnomad4 OTH AF: 0.158

Alfa AF: 0.139 Hom.: 327

Bravo AF: 0.160

Asia WGS AF: 0.269 AC: 934 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

Occult macular dystrophy Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jan 12, 2018

This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -

not provided Benign:1

Benign, criteria provided, single submitter

not provided

Breakthrough Genomics, Breakthrough Genomics

-

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	0.32
DANN	Benign	0.42

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

Publications

LitVar

Other links and lift over

dbSNP: rs60196627; hg19: chr8-10464075;