dbSNP rs3836573: SCARB2:c.1399-169_1399-167delCTG (chr4-76161917-TCAG-T) – ACMG Classification: Benign (-10 pts)

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_ModerateBA1

The NM_005506.4(SCARB2):c.1399-169_1399-167delCTG variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.29 in 691,440 control chromosomes in the GnomAD database, including 37,294 homozygotes. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.36 ( 12799 hom., cov: 0)

Exomes 𝑓: 0.27 ( 24495 hom. )

Consequence

SCARB2
NM_005506.4 intron

Scores

Not classified

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.558

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:

ENSG00000286074 (HGNC:):

ENSG00000286074 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -10 ACMG points.

BP6

Variant 4-76161917-TCAG-T is Benign according to our data. Variant chr4-76161917-TCAG-T is described in ClinVar as [Benign]. Clinvar id is 670900.Status of the report is criteria_provided_single_submitter, 1 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.652 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein	UniProt
SCARB2	NM_005506.4 link	c.1399-169_1399-167delCTG	intron_variant	Intron 11 of 11	ENST00000264896.8	NP_005497.1	Q14108-1A0A024RDG6
SCARB2	NM_001204255.2 link	c.970-169_970-167delCTG	intron_variant	Intron 8 of 8		NP_001191184.1	Q14108-2
SCARB2	XM_047416429.1 link	c.925-169_925-167delCTG	intron_variant	Intron 11 of 11		XP_047272385.1
SCARB2	XM_047416430.1 link	c.925-169_925-167delCTG	intron_variant	Intron 11 of 11		XP_047272386.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SCARB2	ENST00000264896.8 link	c.1399-169_1399-167delCTG		intron_variant	Intron 11 of 11	1	NM_005506.4	ENSP00000264896.2		Q14108-1

Frequencies

GnomAD3 genomes

AF:

0.359

AC:

54368

AN:

151448

Hom.:

12744

Cov.:

show subpopulations

Gnomad AFR

AF:

0.658

Gnomad AMI

AF:

0.289

Gnomad AMR

AF:

0.257

Gnomad ASJ

AF:

0.274

Gnomad EAS

AF:

0.611

Gnomad SAS

AF:

0.378

Gnomad FIN

AF:

0.249

Gnomad MID

AF:

0.247

Gnomad NFE

AF:

0.205

Gnomad OTH

AF:

0.320

GnomAD4 exome

AF:

0.271

AC:

146044

AN:

539874

Hom.:

24495

AF XY:

0.274

AC XY:

79354

AN XY:

289922

show subpopulations

Gnomad4 AFR exome

AF:

0.657

Gnomad4 AMR exome

AF:

0.261

Gnomad4 ASJ exome

AF:

0.284

Gnomad4 EAS exome

AF:

0.618

Gnomad4 SAS exome

AF:

0.364

Gnomad4 FIN exome

AF:

0.255

Gnomad4 NFE exome

AF:

0.202

Gnomad4 OTH exome

AF:

0.276

GnomAD4 genome

AF:

0.360

AC:

54493

AN:

151566

Hom.:

12799

Cov.:

AF XY:

0.362

AC XY:

26793

AN XY:

74058

show subpopulations

Gnomad4 AFR

AF:

0.658

Gnomad4 AMR

AF:

0.258

Gnomad4 ASJ

AF:

0.274

Gnomad4 EAS

AF:

0.611

Gnomad4 SAS

AF:

0.378

Gnomad4 FIN

AF:

0.249

Gnomad4 NFE

AF:

0.205

Gnomad4 OTH

AF:

0.325

Alfa

AF:

0.294

Hom.:

1063

Bravo

AF:

0.373

Asia WGS

AF:

0.532

AC:

1847

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Jun 18, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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

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