22-20425532-G-C

Position:

• chr22-20425532-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.2444C>G​(p.Ala815Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.346 in 1,341,348 control chromosomes in the GnomAD database, including 83,597 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 0.33 (8753 hom., cov: 32)
  • Exomes 𝑓: 0.35 (74844 hom.)
• Consequence: SCARF2 NM_182895.5 missense
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:6
• Conservation: PhyloP100: 0.751

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=8.164644E-4).
• BP6: Variant 22-20425532-G-C is Benign according to our data. Variant chr22-20425532-G-C is described in ClinVar as [Benign]. Clinvar id is 518325.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr22-20425532-G-C is described in Lovd as [Benign].
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.362 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SCARF2	NM_182895.5	c.2444C>G	p.Ala815Gly	missense_variant	11/11	ENST00000622235.5	NP_878315.2
SCARF2	NM_153334.7	c.2459C>G	p.Ala820Gly	missense_variant	11/11		NP_699165.3
SCARF2	XM_047441585.1	c.2558C>G	p.Ala853Gly	missense_variant	11/11		XP_047297541.1
SCARF2	XM_017029065.3	c.*673C>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.2444C>G	p.Ala815Gly	missense_variant	11/11	1	NM_182895.5	ENSP00000477564.2
SCARF2	ENST00000623402.1	c.2459C>G	p.Ala820Gly	missense_variant	11/11	1		ENSP00000485276.1

Frequencies

GnomAD3 genomes AF: 0.332 AC: 50301 AN: 151642 Hom.: 8755 Cov.: 32

Gnomad AFR AF: 0.325

Gnomad AMI AF: 0.340

Gnomad AMR AF: 0.267

Gnomad ASJ AF: 0.359

Gnomad EAS AF: 0.0585

Gnomad SAS AF: 0.170

Gnomad FIN AF: 0.435

Gnomad MID AF: 0.299

Gnomad NFE AF: 0.366

Gnomad OTH AF: 0.313

GnomAD3 exomes AF: 0.301 AC: 7826 AN: 25994 Hom.: 1184 AF XY: 0.309 AC XY: 4775 AN XY: 15464

Gnomad AFR exome AF: 0.312

Gnomad AMR exome AF: 0.150

Gnomad ASJ exome AF: 0.371

Gnomad EAS exome AF: 0.0733

Gnomad SAS exome AF: 0.175

Gnomad FIN exome AF: 0.412

Gnomad NFE exome AF: 0.363

Gnomad OTH exome AF: 0.368

GnomAD4 exome AF: 0.348 AC: 414113 AN: 1189596 Hom.: 74844 Cov.: 39 AF XY: 0.345 AC XY: 198299 AN XY: 575466

Gnomad4 AFR exome AF: 0.320

Gnomad4 AMR exome AF: 0.203

Gnomad4 ASJ exome AF: 0.361

Gnomad4 EAS exome AF: 0.0559

Gnomad4 SAS exome AF: 0.179

Gnomad4 FIN exome AF: 0.414

Gnomad4 NFE exome AF: 0.367

Gnomad4 OTH exome AF: 0.323

GnomAD4 genome AF: 0.332 AC: 50313 AN: 151752 Hom.: 8753 Cov.: 32 AF XY: 0.330 AC XY: 24467 AN XY: 74182

Gnomad4 AFR AF: 0.325

Gnomad4 AMR AF: 0.267

Gnomad4 ASJ AF: 0.359

Gnomad4 EAS AF: 0.0587

Gnomad4 SAS AF: 0.170

Gnomad4 FIN AF: 0.435

Gnomad4 NFE AF: 0.366

Gnomad4 OTH AF: 0.309

Alfa AF: 0.200 Hom.: 403

Bravo AF: 0.319

TwinsUK AF: 0.375 AC: 1391

ALSPAC AF: 0.362 AC: 1395

ESP6500AA AF: 0.264 AC: 630

ESP6500EA AF: 0.298 AC: 1652

ExAC AF: 0.218 AC: 21089

Asia WGS AF: 0.119 AC: 410 AN: 3454

ClinVar

Significance: Benign

Submissions summary: Benign:6

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:3

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Sep 05, 2019	- -
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	-	- -

not specified Benign:1

Benign, no assertion criteria provided

clinical testing

Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.072
BayesDel_addAF	Benign	-0.75	T
BayesDel_noAF	Benign	-0.70
CADD	Benign	9.6
DANN	Benign	0.91
Eigen	Benign	-1.1
Eigen_PC	Benign	-1.1
FATHMM_MKL	Benign	0.19	N
LIST_S2	Benign	0.41	T;T
MetaRNN	Benign	0.00082	T;T
MetaSVM	Benign	-0.89	T
PrimateAI	Uncertain	0.73	T
Sift4G	Benign	0.40	T;T
Vest4		0.095
ClinPred		0.0052	T
GERP RS		0.076
Varity_R		0.025
gMVP		0.18

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: rs874100; hg19: chr22-20779822; COSMIC: COSV56731038; COSMIC: COSV56731038;