Variant chr4-76161971-C-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_005506.4(SCARB2):c.1399-220G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.011 in 612,698 control chromosomes in the GnomAD database, including 185 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.023 ( 109 hom., cov: 32)

Exomes 𝑓: 0.0069 ( 76 hom. )

Consequence

SCARB2
NM_005506.4 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -0.227

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 links:

(HGNC:):

links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.82).

BP6

Variant 4-76161971-C-A is Benign according to our data. Variant chr4-76161971-C-A is described in ClinVar as [Benign]. Clinvar id is 673157.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0693 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	MANE
SCARB2	NM_005506.4 linkuse as main transcript	c.1399-220G>T	intron_variant	ENST00000264896.8
SCARB2	NM_001204255.2 linkuse as main transcript	c.970-220G>T	intron_variant
SCARB2	XM_047416429.1 linkuse as main transcript	c.925-220G>T	intron_variant
SCARB2	XM_047416430.1 linkuse as main transcript	c.925-220G>T	intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SCARB2	ENST00000264896.8 linkuse as main transcript	c.1399-220G>T		intron_variant		1	NM_005506.4	P4	Q14108-1
	ENST00000651366.1 linkuse as main transcript	n.102+12705C>A		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes

AF:

0.0231

AC:

3516

AN:

152044

Hom.:

109

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0714

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00956

Gnomad ASJ

AF:

0.000288

Gnomad EAS

AF:

0.0505

Gnomad SAS

AF:

0.00601

Gnomad FIN

AF:

0.000849

Gnomad MID

AF:

0.0158

Gnomad NFE

AF:

0.00110

Gnomad OTH

AF:

0.0186

GnomAD4 exome

AF:

0.00691

AC:

3182

AN:

460536

Hom.:

Cov.:

AF XY:

0.00631

AC XY:

1549

AN XY:

245364

show subpopulations

Gnomad4 AFR exome

AF:

0.0696

Gnomad4 AMR exome

AF:

0.00484

Gnomad4 ASJ exome

AF:

0.00140

Gnomad4 EAS exome

AF:

0.0462

Gnomad4 SAS exome

AF:

0.00305

Gnomad4 FIN exome

AF:

0.000763

Gnomad4 NFE exome

AF:

0.00110

Gnomad4 OTH exome

AF:

0.00924

GnomAD4 genome

AF:

0.0232

AC:

3528

AN:

152162

Hom.:

109

Cov.:

AF XY:

0.0229

AC XY:

1704

AN XY:

74402

show subpopulations

Gnomad4 AFR

AF:

0.0714

Gnomad4 AMR

AF:

0.00955

Gnomad4 ASJ

AF:

0.000288

Gnomad4 EAS

AF:

0.0506

Gnomad4 SAS

AF:

0.00601

Gnomad4 FIN

AF:

0.000849

Gnomad4 NFE

AF:

0.00110

Gnomad4 OTH

AF:

0.0189

Alfa

AF:

0.0164

Hom.:

Bravo

AF:

0.0264

Asia WGS

AF:

0.0220

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Jun 14, 2018	This 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

-0.82

CADD

Benign

2.6

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

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

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over