chr4-76162031-G-A

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBA1

The NM_005506.4(SCARB2):​c.1399-280C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0465 in 507,224 control chromosomes in the GnomAD database, including 706 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.041 ( 184 hom., cov: 32)
Exomes 𝑓: 0.049 ( 522 hom. )

Consequence

SCARB2
NM_005506.4 intron

Scores

2

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.178
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]

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -14 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.83).
BP6
Variant 4-76162031-G-A is Benign according to our data. Variant chr4-76162031-G-A is described in ClinVar as [Benign]. Clinvar id is 668971.Status of the report is criteria_provided_single_submitter, 1 stars.
BA1
GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0597 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
SCARB2NM_005506.4 linkuse as main transcriptc.1399-280C>T intron_variant ENST00000264896.8
SCARB2NM_001204255.2 linkuse as main transcriptc.970-280C>T intron_variant
SCARB2XM_047416429.1 linkuse as main transcriptc.925-280C>T intron_variant
SCARB2XM_047416430.1 linkuse as main transcriptc.925-280C>T intron_variant

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
SCARB2ENST00000264896.8 linkuse as main transcriptc.1399-280C>T intron_variant 1 NM_005506.4 P4Q14108-1
ENST00000651366.1 linkuse as main transcriptn.102+12765G>A intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes
AF:
0.0412
AC:
6261
AN:
152096
Hom.:
184
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.0109
Gnomad AMI
AF:
0.170
Gnomad AMR
AF:
0.0375
Gnomad ASJ
AF:
0.00923
Gnomad EAS
AF:
0.000193
Gnomad SAS
AF:
0.0296
Gnomad FIN
AF:
0.0595
Gnomad MID
AF:
0.0601
Gnomad NFE
AF:
0.0613
Gnomad OTH
AF:
0.0411
GnomAD4 exome
AF:
0.0488
AC:
17338
AN:
355010
Hom.:
522
Cov.:
0
AF XY:
0.0479
AC XY:
8972
AN XY:
187240
show subpopulations
Gnomad4 AFR exome
AF:
0.00907
Gnomad4 AMR exome
AF:
0.0318
Gnomad4 ASJ exome
AF:
0.00927
Gnomad4 EAS exome
AF:
0.000171
Gnomad4 SAS exome
AF:
0.0337
Gnomad4 FIN exome
AF:
0.0524
Gnomad4 NFE exome
AF:
0.0620
Gnomad4 OTH exome
AF:
0.0495
GnomAD4 genome
AF:
0.0411
AC:
6260
AN:
152214
Hom.:
184
Cov.:
32
AF XY:
0.0416
AC XY:
3097
AN XY:
74410
show subpopulations
Gnomad4 AFR
AF:
0.0109
Gnomad4 AMR
AF:
0.0374
Gnomad4 ASJ
AF:
0.00923
Gnomad4 EAS
AF:
0.000193
Gnomad4 SAS
AF:
0.0300
Gnomad4 FIN
AF:
0.0595
Gnomad4 NFE
AF:
0.0613
Gnomad4 OTH
AF:
0.0407
Alfa
AF:
0.0492
Hom.:
31
Bravo
AF:
0.0386
Asia WGS
AF:
0.0120
AC:
41
AN:
3478

ClinVar

Significance: Benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not provided Benign:1
Benign, criteria provided, single submitterclinical testingGeneDxJun 19, 2018This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.83
CADD
Benign
6.4
DANN
Benign
0.58

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.030
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

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs72655526; hg19: chr4-77083184; API