rs537247534
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Variant summary
Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_StrongBP6BS1BS2
The ENST00000622235.5(SCARF2):c.2522C>T(p.Thr841Ile) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00116 in 1,418,186 control chromosomes in the GnomAD database, including 6 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).
Frequency
Genomes: 𝑓 0.0012 ( 0 hom., cov: 33)
Exomes 𝑓: 0.0012 ( 6 hom. )
Consequence
SCARF2
ENST00000622235.5 missense
ENST00000622235.5 missense
Scores
3
3
8
Clinical Significance
Conservation
PhyloP100: 8.35
Genes affected
SCARF2 (HGNC:19869): (scavenger receptor class F member 2) The protein encoded by this gene is similar to SCARF1/SREC-I, a scavenger receptor protein that mediates the binding and degradation of acetylated low density lipoprotein (Ac-LDL). This protein has only little activity of internalizing modified low density lipoproteins (LDL), but it can interact with SCARF1 through its extracellular domain. The association of this protein with SCARF1 is suppressed by the presence of scavenger ligands. Alternatively spliced transcript variants encoding distinct isoforms have been reported. [provided by RefSeq, Jul 2008]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -13 ACMG points.
BP4
Computational evidence support a benign effect (MetaRNN=0.007663578).
BP6
Variant 22-20425454-G-A is Benign according to our data. Variant chr22-20425454-G-A is described in ClinVar as [Conflicting_classifications_of_pathogenicity]. Clinvar id is 436646.We mark this variant Likely_benign, oryginal submissions are: {Uncertain_significance=3, Likely_benign=2}.
BS1
Variant frequency is greater than expected in population mid. gnomad4_exome allele frequency = 0.00116 (1463/1266008) while in subpopulation MID AF= 0.0152 (64/4214). AF 95% confidence interval is 0.0122. There are 6 homozygotes in gnomad4_exome. There are 754 alleles in male gnomad4_exome subpopulation. Median coverage is 31. This position pass quality control queck.
BS2
High Homozygotes in GnomAdExome4 at 6 AR gene
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
SCARF2 | NM_182895.5 | c.2522C>T | p.Thr841Ile | missense_variant | 11/11 | ENST00000622235.5 | NP_878315.2 | |
SCARF2 | NM_153334.7 | c.2537C>T | p.Thr846Ile | missense_variant | 11/11 | NP_699165.3 | ||
SCARF2 | XM_047441585.1 | c.2636C>T | p.Thr879Ile | missense_variant | 11/11 | XP_047297541.1 | ||
SCARF2 | XM_017029065.3 | c.*751C>T | 3_prime_UTR_variant | 11/11 | XP_016884554.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
SCARF2 | ENST00000622235.5 | c.2522C>T | p.Thr841Ile | missense_variant | 11/11 | 1 | NM_182895.5 | ENSP00000477564 | P1 | |
SCARF2 | ENST00000623402.1 | c.2537C>T | p.Thr846Ile | missense_variant | 11/11 | 1 | ENSP00000485276 |
Frequencies
GnomAD3 genomes AF: 0.00121 AC: 184AN: 152070Hom.: 0 Cov.: 33
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GnomAD3 exomes AF: 0.00111 AC: 123AN: 111090Hom.: 3 AF XY: 0.00123 AC XY: 80AN XY: 65078
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GnomAD4 exome AF: 0.00116 AC: 1463AN: 1266008Hom.: 6 Cov.: 31 AF XY: 0.00121 AC XY: 754AN XY: 620950
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GnomAD4 genome AF: 0.00122 AC: 185AN: 152178Hom.: 0 Cov.: 33 AF XY: 0.00109 AC XY: 81AN XY: 74414
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ClinVar
Significance: Conflicting classifications of pathogenicity
Submissions summary: Uncertain:3Benign:2
Revision: criteria provided, conflicting classifications
LINK: link
Submissions by phenotype
not provided Uncertain:2Benign:2
Uncertain significance, criteria provided, single submitter | not provided | Breakthrough Genomics, Breakthrough Genomics | - | - - |
Likely benign, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | Dec 13, 2023 | - - |
Uncertain significance, criteria provided, single submitter | clinical testing | Center for Pediatric Genomic Medicine, Children's Mercy Hospital and Clinics | Mar 07, 2017 | - - |
Likely benign, criteria provided, single submitter | clinical testing | CeGaT Center for Human Genetics Tuebingen | Sep 01, 2024 | SCARF2: BS2 - |
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Genetic Services Laboratory, University of Chicago | Apr 08, 2016 | - - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
CADD
Uncertain
DANN
Uncertain
Eigen
Benign
Eigen_PC
Benign
FATHMM_MKL
Pathogenic
D
LIST_S2
Benign
T;T
M_CAP
Uncertain
D
MetaRNN
Benign
T;T
MetaSVM
Benign
T
MutationTaster
Benign
N;N
PrimateAI
Pathogenic
D
Sift4G
Uncertain
D;T
Vest4
MVP
ClinPred
T
GERP RS
RBP_binding_hub_radar
RBP_regulation_power_radar
Varity_R
gMVP
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