rs12542075

Variant names:

• chr8-10606696-G-A
• rs12542075
• NM_178857.6:c.*199C>T

Your query was ambiguous. Multiple possible variants found:

• chr8-10606696-G-A
• chr8-10606696-G-C

Variant summary

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

The NM_178857.6(RP1L1):​c.*199C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.149 in 842,952 control chromosomes in the GnomAD database, including 11,193 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.13 (1676 hom., cov: 34)
  • Exomes 𝑓: 0.15 (9517 hom.)
• Consequence: RP1L1 NM_178857.6 3_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -1.25

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=-0.82).
• BP6: Variant 8-10606696-G-A is Benign according to our data. Variant chr8-10606696-G-A is described in ClinVar as [Benign]. Clinvar id is 361198.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.334 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RP1L1	NM_178857.6	c.*199C>T		3_prime_UTR_variant	Exon 4 of 4	ENST00000382483.4	NP_849188.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RP1L1	ENST00000382483	c.*199C>T		3_prime_UTR_variant	Exon 4 of 4	1	NM_178857.6	ENSP00000371923.3

Frequencies

GnomAD3 genomes AF: 0.131 AC: 20005 AN: 152170 Hom.: 1675 Cov.: 34

Gnomad AFR AF: 0.0561

Gnomad AMI AF: 0.0934

Gnomad AMR AF: 0.156

Gnomad ASJ AF: 0.158

Gnomad EAS AF: 0.174

Gnomad SAS AF: 0.347

Gnomad FIN AF: 0.196

Gnomad MID AF: 0.177

Gnomad NFE AF: 0.142

Gnomad OTH AF: 0.147

GnomAD4 exome AF: 0.153 AC: 105902 AN: 690664 Hom.: 9517 Cov.: 9 AF XY: 0.162 AC XY: 57049 AN XY: 353132

Gnomad4 AFR exome AF: 0.0527

Gnomad4 AMR exome AF: 0.159

Gnomad4 ASJ exome AF: 0.153

Gnomad4 EAS exome AF: 0.182

Gnomad4 SAS exome AF: 0.339

Gnomad4 FIN exome AF: 0.184

Gnomad4 NFE exome AF: 0.134

Gnomad4 OTH exome AF: 0.150

GnomAD4 genome AF: 0.131 AC: 20006 AN: 152288 Hom.: 1676 Cov.: 34 AF XY: 0.140 AC XY: 10429 AN XY: 74470

Gnomad4 AFR AF: 0.0561

Gnomad4 AMR AF: 0.156

Gnomad4 ASJ AF: 0.158

Gnomad4 EAS AF: 0.174

Gnomad4 SAS AF: 0.348

Gnomad4 FIN AF: 0.196

Gnomad4 NFE AF: 0.142

Gnomad4 OTH AF: 0.145

Alfa AF: 0.145 Hom.: 3418

Bravo AF: 0.124

Asia WGS AF: 0.251 AC: 873 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

Occult macular dystrophy Benign:1

Jan 13, 2018

Illumina Laboratory Services, Illumina

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	0.38
DANN	Benign	0.64

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: rs12542075; hg19: chr8-10464206;