rs537247534

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

Scores

3
3
8

Clinical Significance

Conflicting classifications of pathogenicity criteria provided, conflicting classifications U:3B:2

Conservation

PhyloP100: 8.35
Variant links:
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]

Genome browser will be placed here

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
SCARF2NM_182895.5 linkuse as main transcriptc.2522C>T p.Thr841Ile missense_variant 11/11 ENST00000622235.5 NP_878315.2
SCARF2NM_153334.7 linkuse as main transcriptc.2537C>T p.Thr846Ile missense_variant 11/11 NP_699165.3
SCARF2XM_047441585.1 linkuse as main transcriptc.2636C>T p.Thr879Ile missense_variant 11/11 XP_047297541.1
SCARF2XM_017029065.3 linkuse as main transcriptc.*751C>T 3_prime_UTR_variant 11/11 XP_016884554.1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
SCARF2ENST00000622235.5 linkuse as main transcriptc.2522C>T p.Thr841Ile missense_variant 11/111 NM_182895.5 ENSP00000477564 P1Q96GP6-2
SCARF2ENST00000623402.1 linkuse as main transcriptc.2537C>T p.Thr846Ile missense_variant 11/111 ENSP00000485276 Q96GP6-1

Frequencies

GnomAD3 genomes
AF:
0.00121
AC:
184
AN:
152070
Hom.:
0
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.000555
Gnomad AMI
AF:
0.0155
Gnomad AMR
AF:
0.00210
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.000828
Gnomad FIN
AF:
0.0000943
Gnomad MID
AF:
0.0255
Gnomad NFE
AF:
0.00140
Gnomad OTH
AF:
0.00335
GnomAD3 exomes
AF:
0.00111
AC:
123
AN:
111090
Hom.:
3
AF XY:
0.00123
AC XY:
80
AN XY:
65078
show subpopulations
Gnomad AFR exome
AF:
0.000322
Gnomad AMR exome
AF:
0.00146
Gnomad ASJ exome
AF:
0.000269
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00110
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00127
Gnomad OTH exome
AF:
0.00525
GnomAD4 exome
AF:
0.00116
AC:
1463
AN:
1266008
Hom.:
6
Cov.:
31
AF XY:
0.00121
AC XY:
754
AN XY:
620950
show subpopulations
Gnomad4 AFR exome
AF:
0.000760
Gnomad4 AMR exome
AF:
0.00199
Gnomad4 ASJ exome
AF:
0.000153
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.000838
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00118
Gnomad4 OTH exome
AF:
0.00148
GnomAD4 genome
AF:
0.00122
AC:
185
AN:
152178
Hom.:
0
Cov.:
33
AF XY:
0.00109
AC XY:
81
AN XY:
74414
show subpopulations
Gnomad4 AFR
AF:
0.000554
Gnomad4 AMR
AF:
0.00209
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.000829
Gnomad4 FIN
AF:
0.0000943
Gnomad4 NFE
AF:
0.00140
Gnomad4 OTH
AF:
0.00331
Alfa
AF:
0.00139
Hom.:
0
Bravo
AF:
0.00147
ExAC
AF:
0.00104
AC:
118

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 submitternot providedBreakthrough Genomics, Breakthrough Genomics-- -
Likely benign, criteria provided, single submitterclinical testingLabcorp Genetics (formerly Invitae), LabcorpDec 13, 2023- -
Uncertain significance, criteria provided, single submitterclinical testingCenter for Pediatric Genomic Medicine, Children's Mercy Hospital and ClinicsMar 07, 2017- -
Likely benign, criteria provided, single submitterclinical testingCeGaT Center for Human Genetics TuebingenSep 01, 2024SCARF2: BS2 -
not specified Uncertain:1
Uncertain significance, criteria provided, single submitterclinical testingGenetic Services Laboratory, University of ChicagoApr 08, 2016- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
0.60
BayesDel_addAF
Benign
-0.38
T
BayesDel_noAF
Benign
-0.36
CADD
Uncertain
25
DANN
Uncertain
1.0
Eigen
Benign
-0.26
Eigen_PC
Benign
-0.17
FATHMM_MKL
Pathogenic
0.98
D
LIST_S2
Benign
0.62
T;T
M_CAP
Uncertain
0.22
D
MetaRNN
Benign
0.0077
T;T
MetaSVM
Benign
-1.1
T
MutationTaster
Benign
0.81
N;N
PrimateAI
Pathogenic
0.96
D
Sift4G
Uncertain
0.044
D;T
Vest4
0.42
MVP
0.23
ClinPred
0.051
T
GERP RS
2.6
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.7
Varity_R
0.090
gMVP
0.51

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

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs537247534; hg19: chr22-20779744; API