rs537247534

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_StrongBP6BS1BS2

The NM_182895.5(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
NM_182895.5 missense

Scores

Clinical Significance

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

Conservation

PhyloP100: 8.35

Publications

1 publications found

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]

SCARF2 Gene-Disease associations (from GenCC):

van den Ende-Gupta syndrome
Inheritance: AR Classification: DEFINITIVE, STRONG, MODERATE, SUPPORTIVE Submitted by: Orphanet, G2P, Ambry Genetics, Labcorp Genetics (formerly Invitae), PanelApp Australia

SCARF2 links:

ENSG00000305663 (HGNC:):

ENSG00000305663 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -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 VariationId is 436646.

BS1

Variant frequency is greater than expected in population mid. GnomAdExome4 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 GnomAdExome4. There are 754 alleles in the male GnomAdExome4 subpopulation. Median coverage is 31. This position passed quality control check.

BS2

High Homozygotes in GnomAdExome4 at 6 AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_182895.5. 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
	SCARF2	NM_182895.5	MANE Select	c.2522C>T	p.Thr841Ile	missense	Exon 11 of 11	NP_878315.2	Q96GP6-2
	SCARF2	NM_153334.7		c.2537C>T	p.Thr846Ile	missense	Exon 11 of 11	NP_699165.3

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
SCARF2	ENST00000622235.5	TSL:1 MANE Select	c.2522C>T	p.Thr841Ile	missense	Exon 11 of 11	ENSP00000477564.2	Q96GP6-2
SCARF2	ENST00000623402.1	TSL:1	c.2537C>T	p.Thr846Ile	missense	Exon 11 of 11	ENSP00000485276.1	Q96GP6-1
SCARF2	ENST00000925309.1		c.2651C>T	p.Thr884Ile	missense	Exon 11 of 11	ENSP00000595368.1

Frequencies

GnomAD3 genomes

AF:

0.00121

AC:

184

AN:

152070

Hom.:

Cov.:

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

GnomAD2 exomes

AF:

0.00111

AC:

123

AN:

111090

AF XY:

0.00123

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 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.:

Cov.:

AF XY:

0.00121

AC XY:

754

AN XY:

620950

show subpopulations

African (AFR)

AF:

0.000760

AC:

AN:

26320

American (AMR)

AF:

0.00199

AC:

AN:

24122

Ashkenazi Jewish (ASJ)

AF:

0.000153

AC:

AN:

19596

East Asian (EAS)

AF:

0.00

AC:

AN:

30870

South Asian (SAS)

AF:

0.000838

AC:

AN:

62058

European-Finnish (FIN)

AF:

0.00

AC:

AN:

31314

Middle Eastern (MID)

AF:

0.0152

AC:

AN:

4214

European-Non Finnish (NFE)

AF:

0.00118

AC:

1200

AN:

1016330

Other (OTH)

AF:

0.00148

AC:

AN:

51184

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.479

Heterozygous variant carriers

154

232

309

386

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

100

150

200

250

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.00122

AC:

185

AN:

152178

Hom.:

Cov.:

AF XY:

0.00109

AC XY:

AN XY:

74414

show subpopulations

African (AFR)

AF:

0.000554

AC:

AN:

41546

American (AMR)

AF:

0.00209

AC:

AN:

15290

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3468

East Asian (EAS)

AF:

0.00

AC:

AN:

5160

South Asian (SAS)

AF:

0.000829

AC:

AN:

4828

European-Finnish (FIN)

AF:

0.0000943

AC:

AN:

10604

Middle Eastern (MID)

AF:

0.0308

AC:

AN:

292

European-Non Finnish (NFE)

AF:

0.00140

AC:

AN:

67970

Other (OTH)

AF:

0.00331

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.490

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.00139

Hom.:

Bravo

AF:

0.00147

ExAC

AF:

0.00104

AC:

118

ClinVar

ClinVar submissions

Significance:Conflicting classifications of pathogenicity

Revision:criteria provided, conflicting classifications

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (4)

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.60

BayesDel_addAF

Benign

-0.38

BayesDel_noAF

Benign

-0.36

CADD

Uncertain

(source)

DANN

Uncertain

1.0

Eigen

Benign

-0.26

Eigen_PC

Benign

-0.17

FATHMM_MKL

Pathogenic

0.98

LIST_S2

Benign

0.62

M_CAP

Uncertain

0.22

MetaRNN

Benign

0.0077

MetaSVM

Benign

-1.1

PhyloP100

8.3

PrimateAI

Pathogenic

0.96

Sift4G

Uncertain

0.044

Vest4

0.42

MVP

0.23

ClinPred

0.051

GERP RS

2.6

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.090

gMVP

0.51

Mutation Taster

=91/9

polymorphism

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over