12-124815284-C-T

Variant names:

• chr12-124815284-C-T
• rs4765615
• NM_005505.5:c.285-170G>A

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_005505.5(SCARB1):​c.285-170G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.486 in 152,050 control chromosomes in the GnomAD database, including 18,099 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.49 (18099 hom., cov: 33)
• Consequence: SCARB1 NM_005505.5 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -2.75
• Publications: 18 publications found

Genes affected

SCARB1 (HGNC:1664): (scavenger receptor class B member 1) The protein encoded by this gene is a plasma membrane receptor for high density lipoprotein cholesterol (HDL). The encoded protein mediates cholesterol transfer to and from HDL. In addition, this protein is a receptor for hepatitis C virus glycoprotein E2 and facilitates cell entry by the virus, SARS-CoV2. [provided by RefSeq, Oct 2021]

ACMG classification

Our verdict: Benign. The variant received -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.79).
• BP6: Variant 12-124815284-C-T is Benign according to our data. Variant chr12-124815284-C-T is described in ClinVar as Benign. ClinVar VariationId is 1181708.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.508 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_005505.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SCARB1	NM_005505.5	MANE Select	c.285-170G>A		intron	N/A	NP_005496.4
	SCARB1	NM_001367981.1		c.285-170G>A		intron	N/A	NP_001354910.1
	SCARB1	NM_001367982.1		c.162-170G>A		intron	N/A	NP_001354911.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SCARB1	ENST00000261693.11	TSL:1 MANE Select	c.285-170G>A		intron	N/A	ENSP00000261693.6
	SCARB1	ENST00000546215.5	TSL:1	c.285-170G>A		intron	N/A	ENSP00000442862.1
	SCARB1	ENST00000535005.5	TSL:1	n.600-170G>A		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.486 AC: 73847 AN: 151932 Hom.: 18087 Cov.: 33

Gnomad AFR AF: 0.475

Gnomad AMI AF: 0.434

Gnomad AMR AF: 0.473

Gnomad ASJ AF: 0.443

Gnomad EAS AF: 0.349

Gnomad SAS AF: 0.424

Gnomad FIN AF: 0.490

Gnomad MID AF: 0.472

Gnomad NFE AF: 0.513

Gnomad OTH AF: 0.486

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.486 AC: 73898 AN: 152050 Hom.: 18099 Cov.: 33 AF XY: 0.481 AC XY: 35777 AN XY: 74304

African (AFR) AF: 0.475 AC: 19710 AN: 41462

American (AMR) AF: 0.473 AC: 7238 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.443 AC: 1537 AN: 3468

East Asian (EAS) AF: 0.349 AC: 1804 AN: 5174

South Asian (SAS) AF: 0.424 AC: 2043 AN: 4818

European-Finnish (FIN) AF: 0.490 AC: 5169 AN: 10552

Middle Eastern (MID) AF: 0.469 AC: 138 AN: 294

European-Non Finnish (NFE) AF: 0.513 AC: 34843 AN: 67970

Other (OTH) AF: 0.484 AC: 1022 AN: 2112

Alfa AF: 0.505 Hom.: 24118

Bravo AF: 0.486

Asia WGS AF: 0.393 AC: 1372 AN: 3478

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
CADD	Benign	0.0090
DANN	Uncertain	0.98
PhyloP100		-2.7
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs4765615; hg19: chr12-125299830;