4-76161917-TCAG-T

Position:

• chr4-76161917-TCAG-T

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_Moderate BA1

The NM_005506.4(SCARB2):​c.1399-169_1399-167del 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
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.558

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 -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	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SCARB2	NM_005506.4	c.1399-169_1399-167del		intron_variant		ENST00000264896.8	NP_005497.1
SCARB2	NM_001204255.2	c.970-169_970-167del		intron_variant			NP_001191184.1
SCARB2	XM_047416429.1	c.925-169_925-167del		intron_variant			XP_047272385.1
SCARB2	XM_047416430.1	c.925-169_925-167del		intron_variant			XP_047272386.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SCARB2	ENST00000264896.8	c.1399-169_1399-167del		intron_variant		1	NM_005506.4	ENSP00000264896	P4
	ENST00000651366.1	n.102+12655_102+12657del		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes AF: 0.359 AC: 54368 AN: 151448 Hom.: 12744 Cov.: 0

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

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.: 0 AF XY: 0.362 AC XY: 26793 AN XY: 74058

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

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jun 18, 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

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: rs3836573; hg19: chr4-77083070;