rs894250

Variant names:

• chr4-76208755-C-A
• rs894250
• NM_005506.4:c.117+4672G>T

Your query was ambiguous. Multiple possible variants found:

• chr4-76208755-C-A
• chr4-76208755-C-G
• chr4-76208755-C-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+4672G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.625 in 152,078 control chromosomes in the GnomAD database, including 31,315 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 0.63 (31315 hom., cov: 32)
• Consequence: SCARB2 NM_005506.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.54
• Publications: 2 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 Submitted by: ClinGen
• 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=-0.8).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.918 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SCARB2	NM_005506.4	c.117+4672G>T		intron_variant	Intron 1 of 11	ENST00000264896.8	NP_005497.1
SCARB2	NM_001204255.2	c.117+4672G>T		intron_variant	Intron 1 of 8		NP_001191184.1
SCARB2	XM_047416429.1	c.-357-12891G>T		intron_variant	Intron 1 of 11		XP_047272385.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SCARB2	ENST00000264896.8	c.117+4672G>T		intron_variant	Intron 1 of 11	1	NM_005506.4	ENSP00000264896.2

Frequencies

GnomAD3 genomes AF: 0.625 AC: 94991 AN: 151960 Hom.: 31267 Cov.: 32

Gnomad AFR AF: 0.800

Gnomad AMI AF: 0.661

Gnomad AMR AF: 0.686

Gnomad ASJ AF: 0.667

Gnomad EAS AF: 0.940

Gnomad SAS AF: 0.619

Gnomad FIN AF: 0.484

Gnomad MID AF: 0.636

Gnomad NFE AF: 0.501

Gnomad OTH AF: 0.621

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

GnomAD4 genome AF: 0.625 AC: 95099 AN: 152078 Hom.: 31315 Cov.: 32 AF XY: 0.627 AC XY: 46580 AN XY: 74302

African (AFR) AF: 0.800 AC: 33194 AN: 41502

American (AMR) AF: 0.686 AC: 10486 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.667 AC: 2315 AN: 3470

East Asian (EAS) AF: 0.940 AC: 4880 AN: 5194

South Asian (SAS) AF: 0.618 AC: 2970 AN: 4806

European-Finnish (FIN) AF: 0.484 AC: 5099 AN: 10546

Middle Eastern (MID) AF: 0.639 AC: 188 AN: 294

European-Non Finnish (NFE) AF: 0.501 AC: 34055 AN: 67962

Other (OTH) AF: 0.621 AC: 1312 AN: 2114

Alfa AF: 0.550 Hom.: 35291

Bravo AF: 0.650

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	0.13
DANN	Benign	0.63
PhyloP100		-1.5
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: rs894250; hg19: chr4-77129908;