rs45552240
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Variant summary
Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBS1BS2
The NM_016180.5(SLC45A2):c.*24A>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00324 in 1,611,258 control chromosomes in the GnomAD database, including 106 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).
Frequency
Genomes: 𝑓 0.0020 ( 7 hom., cov: 33)
Exomes 𝑓: 0.0034 ( 99 hom. )
Consequence
SLC45A2
NM_016180.5 3_prime_UTR
NM_016180.5 3_prime_UTR
Scores
2
Clinical Significance
Conservation
PhyloP100: 0.151
Genes affected
SLC45A2 (HGNC:16472): (solute carrier family 45 member 2) This gene encodes a transporter protein that mediates melanin synthesis. The protein is expressed in a high percentage of melanoma cell lines. Mutations in this gene are a cause of oculocutaneous albinism type 4, and polymorphisms in this gene are associated with variations in skin and hair color. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Mar 2009]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -14 ACMG points.
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.82).
BP6
?
Variant 5-33944624-T-G is Benign according to our data. Variant chr5-33944624-T-G is described in ClinVar as [Likely_benign]. Clinvar id is 906956.Status of the report is criteria_provided_single_submitter, 1 stars.
BS1
?
Variant frequency is greater than expected in population sas. gnomad4 allele frequency = 0.00204 (311/152274) while in subpopulation SAS AF= 0.0345 (166/4816). AF 95% confidence interval is 0.0302. There are 7 homozygotes in gnomad4. There are 186 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.
BS2
?
High Homozygotes in GnomAd4 at 7 AD,AR gene
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
SLC45A2 | NM_016180.5 | c.*24A>C | 3_prime_UTR_variant | 7/7 | ENST00000296589.9 | ||
SLC45A2 | XM_047417259.1 | c.*24A>C | 3_prime_UTR_variant | 7/7 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
SLC45A2 | ENST00000296589.9 | c.*24A>C | 3_prime_UTR_variant | 7/7 | 1 | NM_016180.5 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.00204 AC: 311AN: 152156Hom.: 7 Cov.: 33
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GnomAD3 exomes AF: 0.00571 AC: 1417AN: 248050Hom.: 35 AF XY: 0.00773 AC XY: 1037AN XY: 134172
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GnomAD4 exome AF: 0.00336 AC: 4903AN: 1458984Hom.: 99 Cov.: 31 AF XY: 0.00452 AC XY: 3278AN XY: 725850
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GnomAD4 genome ? AF: 0.00204 AC: 311AN: 152274Hom.: 7 Cov.: 33 AF XY: 0.00250 AC XY: 186AN XY: 74466
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ClinVar
Significance: Likely benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
Oculocutaneous albinism type 4 Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Jan 13, 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 likely benign is not then subjected to further curation. The score for this variant resulted in a classification of likely benign for this disease. - |
Computational scores
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Name
Calibrated prediction
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BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at