NM_005505.5:c.726+54C>T

Variant names:

• chr12-124811816-G-A
• rs61932577
• NM_005505.5:c.726+54C>T

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_005505.5(SCARB1):​c.726+54C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0822 in 1,298,030 control chromosomes in the GnomAD database, including 5,172 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.062 (440 hom., cov: 32)
  • Exomes 𝑓: 0.085 (4732 hom.)
• Consequence: SCARB1 NM_005505.5 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -4.80
• Publications: 16 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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.07).
• BP6: Variant 12-124811816-G-A is Benign according to our data. Variant chr12-124811816-G-A is described in ClinVar as Benign. ClinVar VariationId is 1250072.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0954 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SCARB1	NM_005505.5	MANE Select	c.726+54C>T		intron	N/A	NP_005496.4
	SCARB1	NM_001367981.1		c.726+54C>T		intron	N/A	NP_001354910.1	Q8WTV0-1
	SCARB1	NM_001367982.1		c.603+54C>T		intron	N/A	NP_001354911.1	B3KW46

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SCARB1	ENST00000261693.11	TSL:1 MANE Select	c.726+54C>T		intron	N/A	ENSP00000261693.6	Q8WTV0-2
	SCARB1	ENST00000546215.5	TSL:1	c.726+54C>T		intron	N/A	ENSP00000442862.1	B7ZKQ9
	SCARB1	ENST00000535005.5	TSL:1	n.1041+54C>T		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.0618 AC: 9396 AN: 151948 Hom.: 440 Cov.: 32

Gnomad AFR AF: 0.0171

Gnomad AMI AF: 0.0515

Gnomad AMR AF: 0.0711

Gnomad ASJ AF: 0.0648

Gnomad EAS AF: 0.00135

Gnomad SAS AF: 0.0287

Gnomad FIN AF: 0.0376

Gnomad MID AF: 0.0892

Gnomad NFE AF: 0.0974

Gnomad OTH AF: 0.0693

GnomAD4 exome AF: 0.0849 AC: 97260 AN: 1145964 Hom.: 4732 AF XY: 0.0834 AC XY: 48374 AN XY: 580350

African (AFR) AF: 0.0152 AC: 400 AN: 26302

American (AMR) AF: 0.0519 AC: 2028 AN: 39102

Ashkenazi Jewish (ASJ) AF: 0.0697 AC: 1658 AN: 23772

East Asian (EAS) AF: 0.000141 AC: 5 AN: 35402

South Asian (SAS) AF: 0.0304 AC: 2301 AN: 75746

European-Finnish (FIN) AF: 0.0451 AC: 2254 AN: 49974

Middle Eastern (MID) AF: 0.0750 AC: 390 AN: 5198

European-Non Finnish (NFE) AF: 0.100 AC: 84407 AN: 840758

Other (OTH) AF: 0.0768 AC: 3817 AN: 49710

GnomAD4 genome AF: 0.0618 AC: 9391 AN: 152066 Hom.: 440 Cov.: 32 AF XY: 0.0577 AC XY: 4290 AN XY: 74328

African (AFR) AF: 0.0170 AC: 706 AN: 41494

American (AMR) AF: 0.0710 AC: 1085 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.0648 AC: 225 AN: 3470

East Asian (EAS) AF: 0.00136 AC: 7 AN: 5166

South Asian (SAS) AF: 0.0285 AC: 137 AN: 4804

European-Finnish (FIN) AF: 0.0376 AC: 398 AN: 10594

Middle Eastern (MID) AF: 0.0925 AC: 27 AN: 292

European-Non Finnish (NFE) AF: 0.0973 AC: 6614 AN: 67942

Other (OTH) AF: 0.0686 AC: 145 AN: 2114

Alfa AF: 0.0322 Hom.: 28

Bravo AF: 0.0622

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.1
CADD	Benign	0.26
DANN	Benign	0.90
PhyloP100		-4.8
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: rs61932577; hg19: chr12-125296362;