chr12-124786183-A-G

Variant names:

• chr12-124786183-A-G
• rs75289200
• NM_005505.5:c.1401+174T>C

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BS1 BS2

The NM_005505.5(SCARB1):​c.1401+174T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00128 in 1,585,040 control chromosomes in the GnomAD database, including 37 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0064 (17 hom., cov: 33)
  • Exomes 𝑓: 0.00073 (20 hom.)
• Consequence: SCARB1 NM_005505.5 intron
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.791
• Publications: 1 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=-0.85).
• BP6: Variant 12-124786183-A-G is Benign according to our data. Variant chr12-124786183-A-G is described in ClinVar as [Likely_benign]. Clinvar id is 1316820.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.00645 (982/152330) while in subpopulation AFR AF = 0.0225 (936/41566). AF 95% confidence interval is 0.0213. There are 17 homozygotes in GnomAd4. There are 432 alleles in the male GnomAd4 subpopulation. Median coverage is 33. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 17 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SCARB1	NM_005505.5	c.1401+174T>C		intron_variant	Intron 11 of 12	ENST00000261693.11	NP_005496.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SCARB1	ENST00000261693.11	c.1401+174T>C		intron_variant	Intron 11 of 12	1	NM_005505.5	ENSP00000261693.6

Frequencies

GnomAD3 genomes AF: 0.00638 AC: 971 AN: 152212 Hom.: 13 Cov.: 33

Gnomad AFR AF: 0.0223

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00236

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000588

Gnomad OTH AF: 0.00287

GnomAD2 exomes AF: 0.00148 AC: 303 AN: 205010 AF XY: 0.00107

Gnomad AFR exome AF: 0.0230

Gnomad AMR exome AF: 0.000659

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000436

Gnomad OTH exome AF: 0.00130

GnomAD4 exome AF: 0.000728 AC: 1043 AN: 1432710 Hom.: 20 Cov.: 31 AF XY: 0.000616 AC XY: 439 AN XY: 712102

African (AFR) AF: 0.0253 AC: 838 AN: 33146

American (AMR) AF: 0.000896 AC: 38 AN: 42434

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25806

East Asian (EAS) AF: 0.00 AC: 0 AN: 39010

South Asian (SAS) AF: 0.0000118 AC: 1 AN: 84978

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 37198

Middle Eastern (MID) AF: 0.00104 AC: 6 AN: 5746

European-Non Finnish (NFE) AF: 0.0000290 AC: 32 AN: 1104694

Other (OTH) AF: 0.00214 AC: 128 AN: 59698

GnomAD4 genome AF: 0.00645 AC: 982 AN: 152330 Hom.: 17 Cov.: 33 AF XY: 0.00580 AC XY: 432 AN XY: 74484

African (AFR) AF: 0.0225 AC: 936 AN: 41566

American (AMR) AF: 0.00235 AC: 36 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5182

South Asian (SAS) AF: 0.00 AC: 0 AN: 4826

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10630

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.0000588 AC: 4 AN: 68036

Other (OTH) AF: 0.00284 AC: 6 AN: 2112

Alfa AF: 0.00381 Hom.: 2

Bravo AF: 0.00730

Asia WGS AF: 0.00520 AC: 18 AN: 3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Apr 21, 2019

GeneDx

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	3.7
DANN	Benign	0.38
PhyloP100		0.79
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.3
Mutation Taster		=100/0	polymorphism

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: rs75289200; hg19: chr12-125270729;