rs6532244

Variant names:

• chr4-76204725-C-A
• rs6532244
• NM_005506.4:c.117+8702G>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_005506.4(SCARB2):​c.117+8702G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.449 in 151,866 control chromosomes in the GnomAD database, including 16,584 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.45 (16584 hom., cov: 31)
• Consequence: SCARB2 NM_005506.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.277
• Publications: 3 publications found

Genes affected

SCARB2 (HGNC:1665): (scavenger receptor class B member 2) The protein encoded by this gene is a type III glycoprotein that is located primarily in limiting membranes of lysosomes and endosomes. Earlier studies in mice and rat suggested that this protein may participate in membrane transportation and the reorganization of endosomal/lysosomal compartment. The protein deficiency in mice was reported to impair cell membrane transport processes and cause pelvic junction obstruction, deafness, and peripheral neuropathy. Further studies in human showed that this protein is a ubiquitously expressed protein and that it is involved in the pathogenesis of HFMD (hand, foot, and mouth disease) caused by enterovirus-71 and possibly by coxsackievirus A16. Mutations in this gene caused an autosomal recessive progressive myoclonic epilepsy-4 (EPM4), also known as action myoclonus-renal failure syndrome (AMRF). Alternatively spliced transcript variants encoding different isoforms have been found for this gene.[provided by RefSeq, Feb 2011]

SCARB2 Gene-Disease associations (from GenCC):

• action myoclonus-renal failure syndrome

  Inheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Ambry Genetics, Orphanet, Labcorp Genetics (formerly Invitae)
• progressive myoclonus epilepsy

  Inheritance: AR Classification: DEFINITIVE, STRONG Submitted by: ClinGen, PanelApp Australia
• Unverricht-Lundborg syndrome

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.896 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_005506.4. 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
	SCARB2	NM_005506.4	MANE Select	c.117+8702G>T		intron	N/A	NP_005497.1	Q14108-1
	SCARB2	NM_001204255.2		c.117+8702G>T		intron	N/A	NP_001191184.1	Q14108-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SCARB2	ENST00000264896.8	TSL:1 MANE Select	c.117+8702G>T		intron	N/A	ENSP00000264896.2	Q14108-1
	SCARB2	ENST00000640634.1	TSL:5	c.93+8702G>T		intron	N/A	ENSP00000492737.1	A0A1W2PRS1
	SCARB2	ENST00000862445.1		c.117+8702G>T		intron	N/A	ENSP00000532504.1

Frequencies

GnomAD3 genomes AF: 0.448 AC: 68053 AN: 151748 Hom.: 16541 Cov.: 31

Gnomad AFR AF: 0.558

Gnomad AMI AF: 0.567

Gnomad AMR AF: 0.457

Gnomad ASJ AF: 0.467

Gnomad EAS AF: 0.918

Gnomad SAS AF: 0.522

Gnomad FIN AF: 0.362

Gnomad MID AF: 0.313

Gnomad NFE AF: 0.351

Gnomad OTH AF: 0.425

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.449 AC: 68157 AN: 151866 Hom.: 16584 Cov.: 31 AF XY: 0.452 AC XY: 33558 AN XY: 74222

African (AFR) AF: 0.558 AC: 23117 AN: 41392

American (AMR) AF: 0.458 AC: 6983 AN: 15242

Ashkenazi Jewish (ASJ) AF: 0.467 AC: 1616 AN: 3464

East Asian (EAS) AF: 0.918 AC: 4742 AN: 5168

South Asian (SAS) AF: 0.521 AC: 2504 AN: 4806

European-Finnish (FIN) AF: 0.362 AC: 3819 AN: 10538

Middle Eastern (MID) AF: 0.330 AC: 97 AN: 294

European-Non Finnish (NFE) AF: 0.351 AC: 23859 AN: 67950

Other (OTH) AF: 0.430 AC: 906 AN: 2106

Alfa AF: 0.389 Hom.: 15726

Bravo AF: 0.461

Asia WGS AF: 0.711 AC: 2470 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	4.7
DANN	Benign	0.55
PhyloP100		0.28
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs6532244; hg19: chr4-77125878;