rs41284767

Positions:

• chr4-76174062-C-T

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The ENST00000264896.8(SCARB2):​c.994+82G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.164 in 1,545,008 control chromosomes in the GnomAD database, including 24,111 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.22 (4677 hom., cov: 32)
  • Exomes 𝑓: 0.16 (19434 hom.)
• Consequence: SCARB2 ENST00000264896.8 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -1.33

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]

(HGNC:):

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.02).
• BP6: Variant 4-76174062-C-T is Benign according to our data. Variant chr4-76174062-C-T is described in ClinVar as [Benign]. Clinvar id is 1178406.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.383 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SCARB2	NM_005506.4	c.994+82G>A		intron_variant		ENST00000264896.8	NP_005497.1
SCARB2	NM_001204255.2	c.565+82G>A		intron_variant			NP_001191184.1
SCARB2	XM_047416429.1	c.520+82G>A		intron_variant			XP_047272385.1
SCARB2	XM_047416430.1	c.520+82G>A		intron_variant			XP_047272386.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SCARB2	ENST00000264896.8	c.994+82G>A		intron_variant		1	NM_005506.4	ENSP00000264896	P4
	ENST00000651366.1	n.102+24796C>T		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes AF: 0.224 AC: 34012 AN: 151874 Hom.: 4659 Cov.: 32

Gnomad AFR AF: 0.388

Gnomad AMI AF: 0.250

Gnomad AMR AF: 0.167

Gnomad ASJ AF: 0.167

Gnomad EAS AF: 0.352

Gnomad SAS AF: 0.188

Gnomad FIN AF: 0.139

Gnomad MID AF: 0.166

Gnomad NFE AF: 0.146

Gnomad OTH AF: 0.210

GnomAD4 exome AF: 0.158 AC: 220055 AN: 1393018 Hom.: 19434 Cov.: 22 AF XY: 0.159 AC XY: 110505 AN XY: 696560

Gnomad4 AFR exome AF: 0.391

Gnomad4 AMR exome AF: 0.155

Gnomad4 ASJ exome AF: 0.169

Gnomad4 EAS exome AF: 0.339

Gnomad4 SAS exome AF: 0.174

Gnomad4 FIN exome AF: 0.134

Gnomad4 NFE exome AF: 0.143

Gnomad4 OTH exome AF: 0.169

GnomAD4 genome AF: 0.224 AC: 34053 AN: 151990 Hom.: 4677 Cov.: 32 AF XY: 0.223 AC XY: 16568 AN XY: 74288

Gnomad4 AFR AF: 0.388

Gnomad4 AMR AF: 0.167

Gnomad4 ASJ AF: 0.167

Gnomad4 EAS AF: 0.351

Gnomad4 SAS AF: 0.187

Gnomad4 FIN AF: 0.139

Gnomad4 NFE AF: 0.146

Gnomad4 OTH AF: 0.211

Alfa AF: 0.184 Hom.: 391

Bravo AF: 0.234

Asia WGS AF: 0.263 AC: 911 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

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 25, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	1.6
DANN	Benign	0.74

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

Other links and lift over

dbSNP: rs41284767; hg19: chr4-77095215; COSMIC: COSV53669935; COSMIC: COSV53669935;