rs76472118

Positions:

• chr22-20427438-G-A

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BS1 BS2

The NM_182895.5(SCARF2):​c.1653C>T​(p.Asp551=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00256 in 1,614,176 control chromosomes in the GnomAD database, including 51 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0045 (3 hom., cov: 33)
  • Exomes 𝑓: 0.0024 (48 hom.)
• Consequence: SCARF2 NM_182895.5 synonymous
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: 1.62

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]

ACMG classification

Verdict is Benign. Variant got -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.5).
• BP6: Variant 22-20427438-G-A is Benign according to our data. Variant chr22-20427438-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 436647.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=1.62 with no splicing effect.
• BS1: Variant frequency is greater than expected in population sas. gnomad4 allele frequency = 0.00452 (689/152348) while in subpopulation SAS AF= 0.0135 (65/4824). AF 95% confidence interval is 0.0108. There are 3 homozygotes in gnomad4. There are 338 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd4 at 3 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SCARF2	NM_182895.5	c.1653C>T	p.Asp551=	synonymous_variant	10/11	ENST00000622235.5
SCARF2	XM_017029065.3	c.1736C>T	p.Thr579Ile	missense_variant	10/11
SCARF2	NM_153334.7	c.1668C>T	p.Asp556=	synonymous_variant	10/11
SCARF2	XM_047441585.1	c.1767C>T	p.Asp589=	synonymous_variant	10/11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SCARF2	ENST00000622235.5	c.1653C>T	p.Asp551=	synonymous_variant	10/11	1	NM_182895.5	P1
SCARF2	ENST00000623402.1	c.1668C>T	p.Asp556=	synonymous_variant	10/11	1
SCARF2	ENST00000494535.1	n.544C>T		non_coding_transcript_exon_variant	4/5	2

Frequencies

GnomAD3 genomes AF: 0.00452 AC: 688 AN: 152230 Hom.: 3 Cov.: 33

Gnomad AFR AF: 0.00907

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00759

Gnomad ASJ AF: 0.0147

Gnomad EAS AF: 0.000192

Gnomad SAS AF: 0.0137

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.0190

Gnomad NFE AF: 0.000853

Gnomad OTH AF: 0.00669

GnomAD3 exomes AF: 0.00413 AC: 1039 AN: 251366 Hom.: 16 AF XY: 0.00465 AC XY: 632 AN XY: 135854

Gnomad AFR exome AF: 0.00886

Gnomad AMR exome AF: 0.00286

Gnomad ASJ exome AF: 0.0131

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.0170

Gnomad FIN exome AF: 0.0000462

Gnomad NFE exome AF: 0.000985

Gnomad OTH exome AF: 0.00521

GnomAD4 exome AF: 0.00236 AC: 3451 AN: 1461828 Hom.: 48 Cov.: 32 AF XY: 0.00285 AC XY: 2073 AN XY: 727196

Gnomad4 AFR exome AF: 0.0110

Gnomad4 AMR exome AF: 0.00347

Gnomad4 ASJ exome AF: 0.0135

Gnomad4 EAS exome AF: 0.0000504

Gnomad4 SAS exome AF: 0.0172

Gnomad4 FIN exome AF: 0.0000562

Gnomad4 NFE exome AF: 0.000696

Gnomad4 OTH exome AF: 0.00426

GnomAD4 genome AF: 0.00452 AC: 689 AN: 152348 Hom.: 3 Cov.: 33 AF XY: 0.00454 AC XY: 338 AN XY: 74494

Gnomad4 AFR AF: 0.00911

Gnomad4 AMR AF: 0.00758

Gnomad4 ASJ AF: 0.0147

Gnomad4 EAS AF: 0.000193

Gnomad4 SAS AF: 0.0135

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000853

Gnomad4 OTH AF: 0.00662

Alfa AF: 0.00338 Hom.: 3

Bravo AF: 0.00510

Asia WGS AF: 0.00779 AC: 27 AN: 3478

EpiCase AF: 0.00191

EpiControl AF: 0.00136

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Likely benign, criteria provided, single submitter	clinical testing	GeneDx	Oct 15, 2020	- -
Benign, criteria provided, single submitter	clinical testing	Invitae	Jan 15, 2024	- -

not specified Benign:1

Benign, criteria provided, single submitter

clinical testing

Genetic Services Laboratory, University of Chicago

Jun 09, 2017

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.50
CADD	Benign	7.8
DANN	Benign	0.80

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

Other links and lift over

dbSNP: rs76472118; hg19: chr22-20781725;