chr4-76161743-C-T
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Variant summary
Our verdict is Benign. Variant got -11 ACMG points: 2P and 13B. PM2BP4_StrongBP6_Very_StrongBP7
The NM_005506.4(SCARB2):c.1407G>A(p.Ala469=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000366 in 1,614,128 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).
Frequency
Genomes: 𝑓 0.00011 ( 1 hom., cov: 32)
Exomes 𝑓: 0.000029 ( 0 hom. )
Consequence
SCARB2
NM_005506.4 synonymous
NM_005506.4 synonymous
Scores
6
Clinical Significance
Conservation
PhyloP100: -0.598
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]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -11 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.037112027).
BP6
Variant 4-76161743-C-T is Benign according to our data. Variant chr4-76161743-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 462921.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BP7
Synonymous conserved (PhyloP=-0.598 with no splicing effect.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
SCARB2 | NM_005506.4 | c.1407G>A | p.Ala469= | synonymous_variant | 12/12 | ENST00000264896.8 | |
SCARB2 | NM_001204255.2 | c.978G>A | p.Ala326= | synonymous_variant | 9/9 | ||
SCARB2 | XM_047416429.1 | c.933G>A | p.Ala311= | synonymous_variant | 12/12 | ||
SCARB2 | XM_047416430.1 | c.933G>A | p.Ala311= | synonymous_variant | 12/12 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
SCARB2 | ENST00000264896.8 | c.1407G>A | p.Ala469= | synonymous_variant | 12/12 | 1 | NM_005506.4 | P4 | |
ENST00000651366.1 | n.102+12477C>T | intron_variant, non_coding_transcript_variant |
Frequencies
GnomAD3 genomes AF: 0.000112 AC: 17AN: 152142Hom.: 1 Cov.: 32
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GnomAD3 exomes AF: 0.0000399 AC: 10AN: 250490Hom.: 0 AF XY: 0.0000590 AC XY: 8AN XY: 135482
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GnomAD4 exome AF: 0.0000287 AC: 42AN: 1461868Hom.: 0 Cov.: 30 AF XY: 0.0000261 AC XY: 19AN XY: 727246
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GnomAD4 genome AF: 0.000112 AC: 17AN: 152260Hom.: 1 Cov.: 32 AF XY: 0.0000672 AC XY: 5AN XY: 74442
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ClinVar
Significance: Likely benign
Submissions summary: Benign:2
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
Inborn genetic diseases Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Ambry Genetics | Mar 09, 2019 | This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. - |
Progressive myoclonic epilepsy Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | Nov 27, 2023 | - - |
Computational scores
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BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
FATHMM_MKL
Benign
N
LIST_S2
Benign
T
MetaRNN
Benign
T
MutationTaster
Benign
D;D
GERP RS
RBP_binding_hub_radar
RBP_regulation_power_radar
Splicing
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Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at