rs7816990

Variant names:

• chr8-10606434-A-C
• rs7816990
• NM_178857.6:c.*461T>G

Your query was ambiguous. Multiple possible variants found:

• chr8-10606434-A-C
• chr8-10606434-A-T

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_178857.6(RP1L1):​c.*461T>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 0.662 in 164,978 control chromosomes in the GnomAD database, including 36,956 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.66 (33778 hom., cov: 33)
  • Exomes 𝑓: 0.69 (3178 hom.)
• Consequence: RP1L1 NM_178857.6 3_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.773
• Publications: 10 publications found

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]

RP1L1 Gene-Disease associations (from GenCC):

• occult macular dystrophy

  Inheritance: AD Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Laboratory for Molecular Medicine, Orphanet, G2P, Labcorp Genetics (formerly Invitae), Ambry Genetics
• retinitis pigmentosa

  Inheritance: AD, AR Classification: DEFINITIVE, SUPPORTIVE Submitted by: Orphanet, G2P
• retinitis pigmentosa 88

  Inheritance: AR, SD Classification: STRONG, LIMITED Submitted by: Ambry Genetics, Labcorp Genetics (formerly Invitae), PanelApp Australia
• cone dystrophy

  Inheritance: AR Classification: LIMITED Submitted by: G2P

ACMG classification

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BP6: Variant 8-10606434-A-C is Benign according to our data. Variant chr8-10606434-A-C is described in ClinVar as Benign. ClinVar VariationId is 361187.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.732 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_178857.6. 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
	RP1L1	NM_178857.6	MANE Select	c.*461T>G		3_prime_UTR	Exon 4 of 4	NP_849188.4

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RP1L1	ENST00000382483.4	TSL:1 MANE Select	c.*461T>G		3_prime_UTR	Exon 4 of 4	ENSP00000371923.3	Q8IWN7-1

Frequencies

GnomAD3 genomes AF: 0.660 AC: 100204 AN: 151926 Hom.: 33774 Cov.: 33

Gnomad AFR AF: 0.553

Gnomad AMI AF: 0.779

Gnomad AMR AF: 0.649

Gnomad ASJ AF: 0.711

Gnomad EAS AF: 0.429

Gnomad SAS AF: 0.514

Gnomad FIN AF: 0.745

Gnomad MID AF: 0.658

Gnomad NFE AF: 0.737

Gnomad OTH AF: 0.657

GnomAD4 exome AF: 0.687 AC: 8887 AN: 12934 Hom.: 3178 Cov.: 0 AF XY: 0.675 AC XY: 4503 AN XY: 6670

African (AFR) AF: 0.500 AC: 62 AN: 124

American (AMR) AF: 0.691 AC: 1424 AN: 2062

Ashkenazi Jewish (ASJ) AF: 0.687 AC: 92 AN: 134

East Asian (EAS) AF: 0.371 AC: 205 AN: 552

South Asian (SAS) AF: 0.496 AC: 644 AN: 1298

European-Finnish (FIN) AF: 0.764 AC: 281 AN: 368

Middle Eastern (MID) AF: 0.682 AC: 15 AN: 22

European-Non Finnish (NFE) AF: 0.739 AC: 5682 AN: 7692

Other (OTH) AF: 0.707 AC: 482 AN: 682

GnomAD4 genome AF: 0.659 AC: 100249 AN: 152044 Hom.: 33778 Cov.: 33 AF XY: 0.654 AC XY: 48619 AN XY: 74314

African (AFR) AF: 0.553 AC: 22905 AN: 41440

American (AMR) AF: 0.649 AC: 9915 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.711 AC: 2469 AN: 3472

East Asian (EAS) AF: 0.429 AC: 2223 AN: 5178

South Asian (SAS) AF: 0.514 AC: 2475 AN: 4814

European-Finnish (FIN) AF: 0.745 AC: 7864 AN: 10560

Middle Eastern (MID) AF: 0.667 AC: 196 AN: 294

European-Non Finnish (NFE) AF: 0.737 AC: 50122 AN: 67980

Other (OTH) AF: 0.650 AC: 1371 AN: 2108

Alfa AF: 0.706 Hom.: 70143

Bravo AF: 0.649

Asia WGS AF: 0.456 AC: 1588 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)
-	-	1	Occult macular dystrophy (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	6.4
DANN	Benign	0.72
PhyloP100		0.77
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: rs7816990; hg19: chr8-10463944;