4-76161971-C-G

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_005506.4(SCARB2):​c.1399-220G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000217 in 460,552 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: not found (cov: 32)
Exomes 𝑓: 0.0000022 ( 0 hom. )

Consequence

SCARB2
NM_005506.4 intron

Scores

2

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.227

Publications

0 publications found
Variant links:
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

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -2 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.84).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
SCARB2NM_005506.4 linkc.1399-220G>C intron_variant Intron 11 of 11 ENST00000264896.8 NP_005497.1 Q14108-1A0A024RDG6
SCARB2NM_001204255.2 linkc.970-220G>C intron_variant Intron 8 of 8 NP_001191184.1 Q14108-2
SCARB2XM_047416429.1 linkc.925-220G>C intron_variant Intron 11 of 11 XP_047272385.1
SCARB2XM_047416430.1 linkc.925-220G>C intron_variant Intron 11 of 11 XP_047272386.1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
SCARB2ENST00000264896.8 linkc.1399-220G>C intron_variant Intron 11 of 11 1 NM_005506.4 ENSP00000264896.2 Q14108-1

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
AF:
0.00000217
AC:
1
AN:
460552
Hom.:
0
Cov.:
0
AF XY:
0.00000408
AC XY:
1
AN XY:
245374
show subpopulations
African (AFR)
AF:
0.00
AC:
0
AN:
12944
American (AMR)
AF:
0.00
AC:
0
AN:
23740
Ashkenazi Jewish (ASJ)
AF:
0.00
AC:
0
AN:
14270
East Asian (EAS)
AF:
0.00
AC:
0
AN:
30466
South Asian (SAS)
AF:
0.0000207
AC:
1
AN:
48234
European-Finnish (FIN)
AF:
0.00
AC:
0
AN:
28832
Middle Eastern (MID)
AF:
0.00
AC:
0
AN:
2326
European-Non Finnish (NFE)
AF:
0.00
AC:
0
AN:
273346
Other (OTH)
AF:
0.00
AC:
0
AN:
26394
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.525
Heterozygous variant carriers
0
0
1
1
2
2
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance
GnomAD4 genome
Cov.:
32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.84
CADD
Benign
2.7
DANN
Benign
0.57
PhyloP100
-0.23

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

Other links and lift over

dbSNP: rs75945181; hg19: chr4-77083124; API