rs6532244

Positions:

• chr4-76204725-C-A

Variant summary

Our verdict is Benign. Variant got -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

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]

ACMG classification

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SCARB2	NM_005506.4	c.117+8702G>T		intron_variant		ENST00000264896.8	NP_005497.1
SCARB2	NM_001204255.2	c.117+8702G>T		intron_variant			NP_001191184.1
SCARB2	XM_047416429.1	c.-357-8861G>T		intron_variant			XP_047272385.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SCARB2	ENST00000264896.8	c.117+8702G>T		intron_variant		1	NM_005506.4	ENSP00000264896	P4

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

Gnomad4 AFR AF: 0.558

Gnomad4 AMR AF: 0.458

Gnomad4 ASJ AF: 0.467

Gnomad4 EAS AF: 0.918

Gnomad4 SAS AF: 0.521

Gnomad4 FIN AF: 0.362

Gnomad4 NFE AF: 0.351

Gnomad4 OTH AF: 0.430

Alfa AF: 0.380 Hom.: 11454

Bravo AF: 0.461

Asia WGS AF: 0.711 AC: 2470 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	4.7
DANN	Benign	0.55

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: rs6532244; hg19: chr4-77125878;