22-20425478-G-C

Position:

• chr22-20425478-G-C

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_182895.5(SCARF2):​c.2498C>G​(p.Ala833Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.603 in 1,386,482 control chromosomes in the GnomAD database, including 254,848 homozygotes. In-silico tool predicts a benign outcome for this variant. 10/15 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.60 (27775 hom., cov: 31)
  • Exomes 𝑓: 0.60 (227073 hom.)
• Consequence: SCARF2 NM_182895.5 missense
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:5
• Conservation: PhyloP100: 0.250

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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=4.9788296E-6).
• BP6: Variant 22-20425478-G-C is Benign according to our data. Variant chr22-20425478-G-C is described in ClinVar as [Benign]. Clinvar id is 518324.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr22-20425478-G-C is described in Lovd as [Benign].
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.615 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SCARF2	NM_182895.5	c.2498C>G	p.Ala833Gly	missense_variant	11/11	ENST00000622235.5	NP_878315.2
SCARF2	NM_153334.7	c.2513C>G	p.Ala838Gly	missense_variant	11/11		NP_699165.3
SCARF2	XM_047441585.1	c.2612C>G	p.Ala871Gly	missense_variant	11/11		XP_047297541.1
SCARF2	XM_017029065.3	c.*727C>G		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.2498C>G	p.Ala833Gly	missense_variant	11/11	1	NM_182895.5	ENSP00000477564.2
SCARF2	ENST00000623402.1	c.2513C>G	p.Ala838Gly	missense_variant	11/11	1		ENSP00000485276.1

Frequencies

GnomAD3 genomes AF: 0.600 AC: 91076 AN: 151718 Hom.: 27772 Cov.: 31

Gnomad AFR AF: 0.614

Gnomad AMI AF: 0.451

Gnomad AMR AF: 0.529

Gnomad ASJ AF: 0.628

Gnomad EAS AF: 0.344

Gnomad SAS AF: 0.517

Gnomad FIN AF: 0.691

Gnomad MID AF: 0.580

Gnomad NFE AF: 0.620

Gnomad OTH AF: 0.588

GnomAD3 exomes AF: 0.549 AC: 47156 AN: 85938 Hom.: 13314 AF XY: 0.558 AC XY: 28089 AN XY: 50362

Gnomad AFR exome AF: 0.586

Gnomad AMR exome AF: 0.375

Gnomad ASJ exome AF: 0.634

Gnomad EAS exome AF: 0.311

Gnomad SAS exome AF: 0.522

Gnomad FIN exome AF: 0.661

Gnomad NFE exome AF: 0.606

Gnomad OTH exome AF: 0.586

GnomAD4 exome AF: 0.603 AC: 744641 AN: 1234656 Hom.: 227073 Cov.: 51 AF XY: 0.601 AC XY: 362107 AN XY: 602024

Gnomad4 AFR exome AF: 0.615

Gnomad4 AMR exome AF: 0.424

Gnomad4 ASJ exome AF: 0.626

Gnomad4 EAS exome AF: 0.311

Gnomad4 SAS exome AF: 0.517

Gnomad4 FIN exome AF: 0.674

Gnomad4 NFE exome AF: 0.618

Gnomad4 OTH exome AF: 0.588

GnomAD4 genome AF: 0.600 AC: 91107 AN: 151826 Hom.: 27775 Cov.: 31 AF XY: 0.600 AC XY: 44540 AN XY: 74200

Gnomad4 AFR AF: 0.614

Gnomad4 AMR AF: 0.528

Gnomad4 ASJ AF: 0.628

Gnomad4 EAS AF: 0.344

Gnomad4 SAS AF: 0.516

Gnomad4 FIN AF: 0.691

Gnomad4 NFE AF: 0.620

Gnomad4 OTH AF: 0.580

Alfa AF: 0.614 Hom.: 3581

Bravo AF: 0.583

TwinsUK AF: 0.621 AC: 2301

ALSPAC AF: 0.615 AC: 2370

ESP6500AA AF: 0.663 AC: 1896

ESP6500EA AF: 0.650 AC: 4269

ExAC AF: 0.525 AC: 57285

Asia WGS AF: 0.463 AC: 1601 AN: 3458

ClinVar

Significance: Benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:3

Benign, criteria provided, single submitter	clinical testing	GeneDx	Sep 06, 2018	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 31, 2024	- -

Van den Ende-Gupta syndrome Benign:2

Benign, no assertion criteria provided	clinical testing	Genome Diagnostics Laboratory, Amsterdam University Medical Center	Jan 15, 2016	- -
Benign, no assertion criteria provided	clinical testing	Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen	-	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.074
BayesDel_addAF	Benign	-0.78	T
BayesDel_noAF	Benign	-0.75
CADD	Benign	4.9
DANN	Benign	0.87
Eigen	Benign	-1.2
Eigen_PC	Benign	-1.3
FATHMM_MKL	Benign	0.012	N
LIST_S2	Benign	0.40	T;T
MetaRNN	Benign	0.0000050	T;T
MetaSVM	Benign	-0.94	T
PrimateAI	Uncertain	0.71	T
Sift4G	Benign	0.37	T;T
Vest4		0.034
ClinPred		0.0021	T
GERP RS		-3.1
Varity_R		0.068
gMVP		0.12

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: rs874101; hg19: chr22-20779768; COSMIC: COSV56731196; COSMIC: COSV56731196;