rs2070139

Variant names:

• chr17-28547296-G-A
• rs2070139
• NM_005148.4:c.*1C>T

Your query was ambiguous. Multiple possible variants found:

• chr17-28547296-G-A
• chr17-28547296-G-T

Variant summary

Our verdict is Benign. The variant received -18 ACMG points: 0P and 18B. BP4_Moderate BP6_Very_Strong BA1

The NM_005148.4(UNC119):​c.*1C>T variant causes a 3 prime UTR change. The variant allele was found at a frequency of 0.156 in 1,613,854 control chromosomes in the GnomAD database, including 22,085 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.13 (1652 hom., cov: 32)
  • Exomes 𝑓: 0.16 (20433 hom.)
• Consequence: UNC119 NM_005148.4 3_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:5
• Conservation: PhyloP100: 4.17
• Publications: 13 publications found

Genes affected

UNC119 (HGNC:12565): (unc-119 lipid binding chaperone) This gene is specifically expressed in the photoreceptors in the retina. The encoded product shares strong homology with the C. elegans unc119 protein and it can functionally complement the C. elegans unc119 mutation. It has been localized to the photoreceptor synapses in the outer plexiform layer of the retina, and suggested to play a role in the mechanism of photoreceptor neurotransmitter release through the synaptic vesicle cycle. Two transcript variants encoding different isoforms have been described for this gene. [provided by RefSeq, Jul 2008]

RSKR (HGNC:26314): (ribosomal protein S6 kinase related) Predicted to enable protein kinase activity. Predicted to be involved in protein phosphorylation. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Benign. The variant received -18 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.3).
• BP6: Variant 17-28547296-G-A is Benign according to our data. Variant chr17-28547296-G-A is described in ClinVar as Benign. ClinVar VariationId is 259652.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.183 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
UNC119	NM_005148.4	c.*1C>T		3_prime_UTR_variant	Exon 5 of 5	ENST00000335765.9	NP_005139.1
UNC119	NM_054035.2	c.*328C>T		3_prime_UTR_variant	Exon 4 of 4		NP_473376.1
UNC119	NM_001330166.2	c.*1C>T		3_prime_UTR_variant	Exon 6 of 6		NP_001317095.1
UNC119	XM_011525459.3	c.*507C>T		3_prime_UTR_variant	Exon 3 of 3		XP_011523761.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
UNC119	ENST00000335765.9	c.*1C>T		3_prime_UTR_variant	Exon 5 of 5	1	NM_005148.4	ENSP00000337040.3

Frequencies

GnomAD3 genomes AF: 0.126 AC: 19152 AN: 152078 Hom.: 1652 Cov.: 32

Gnomad AFR AF: 0.0329

Gnomad AMI AF: 0.148

Gnomad AMR AF: 0.117

Gnomad ASJ AF: 0.185

Gnomad EAS AF: 0.00135

Gnomad SAS AF: 0.0379

Gnomad FIN AF: 0.196

Gnomad MID AF: 0.133

Gnomad NFE AF: 0.186

Gnomad OTH AF: 0.145

GnomAD2 exomes AF: 0.131 AC: 32839 AN: 251036 AF XY: 0.133

Gnomad AFR exome AF: 0.0291

Gnomad AMR exome AF: 0.0853

Gnomad ASJ exome AF: 0.192

Gnomad EAS exome AF: 0.000163

Gnomad FIN exome AF: 0.193

Gnomad NFE exome AF: 0.186

Gnomad OTH exome AF: 0.158

GnomAD4 exome AF: 0.159 AC: 232456 AN: 1461658 Hom.: 20433 Cov.: 33 AF XY: 0.157 AC XY: 114343 AN XY: 727122

African (AFR) AF: 0.0259 AC: 867 AN: 33478

American (AMR) AF: 0.0926 AC: 4139 AN: 44712

Ashkenazi Jewish (ASJ) AF: 0.189 AC: 4930 AN: 26128

East Asian (EAS) AF: 0.000277 AC: 11 AN: 39698

South Asian (SAS) AF: 0.0439 AC: 3784 AN: 86254

European-Finnish (FIN) AF: 0.193 AC: 10316 AN: 53376

Middle Eastern (MID) AF: 0.117 AC: 676 AN: 5768

European-Non Finnish (NFE) AF: 0.179 AC: 198535 AN: 1111872

Other (OTH) AF: 0.152 AC: 9198 AN: 60372

GnomAD4 genome AF: 0.126 AC: 19152 AN: 152196 Hom.: 1652 Cov.: 32 AF XY: 0.123 AC XY: 9128 AN XY: 74398

African (AFR) AF: 0.0328 AC: 1364 AN: 41556

American (AMR) AF: 0.117 AC: 1788 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.185 AC: 643 AN: 3468

East Asian (EAS) AF: 0.00135 AC: 7 AN: 5188

South Asian (SAS) AF: 0.0385 AC: 186 AN: 4830

European-Finnish (FIN) AF: 0.196 AC: 2073 AN: 10578

Middle Eastern (MID) AF: 0.133 AC: 39 AN: 294

European-Non Finnish (NFE) AF: 0.186 AC: 12615 AN: 67968

Other (OTH) AF: 0.143 AC: 302 AN: 2108

Alfa AF: 0.161 Hom.: 4826

Bravo AF: 0.120

Asia WGS AF: 0.0280 AC: 98 AN: 3478

EpiCase AF: 0.187

EpiControl AF: 0.196

ClinVar

Significance: Benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:2

Mar 29, 2016

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Variant identified in a genome or exome case(s) and assessed due to predicted null impact of the variant or pathogenic assertions in the literature or databases. Disclaimer: This variant has not undergone full assessment. The following are preliminary notes: Frequency -

-

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Idiopathic CD4 lymphocytopenia Benign:1

May 28, 2019

Mendelics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Cone-rod dystrophy Benign:1

Jan 12, 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	-0.30
CADD	Benign	13
DANN	Benign	0.88
PhyloP100		4.2
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Mutation Taster		=95/5	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: rs2070139; hg19: chr17-26874314;