rs914189

Positions:

• chr21-42290799-C-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000398449.8(ABCG1):​c.1394-293C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.249 in 152,110 control chromosomes in the GnomAD database, including 5,139 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.25 (5139 hom., cov: 32)
• Consequence: ABCG1 ENST00000398449.8 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0300

Genes affected

ABCG1 (HGNC:73): (ATP binding cassette subfamily G member 1) The protein encoded by this gene is a member of the superfamily of ATP-binding cassette (ABC) transporters. ABC proteins transport various molecules across extra- and intra-cellular membranes. ABC genes are divided into seven distinct subfamilies (ABC1, MDR/TAP, MRP, ALD, OABP, GCN20, White). This protein is a member of the White subfamily. It is involved in macrophage cholesterol and phospholipids transport, and may regulate cellular lipid homeostasis in other cell types. Six alternative splice variants have been identified. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.359 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ABCG1	NM_016818.3	c.1394-293C>G		intron_variant		ENST00000398449.8	NP_058198.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ABCG1	ENST00000398449.8	c.1394-293C>G		intron_variant		1	NM_016818.3	ENSP00000381467	P1

Frequencies

GnomAD3 genomes AF: 0.249 AC: 37775 AN: 151992 Hom.: 5122 Cov.: 32

Gnomad AFR AF: 0.364

Gnomad AMI AF: 0.183

Gnomad AMR AF: 0.228

Gnomad ASJ AF: 0.231

Gnomad EAS AF: 0.227

Gnomad SAS AF: 0.167

Gnomad FIN AF: 0.239

Gnomad MID AF: 0.212

Gnomad NFE AF: 0.195

Gnomad OTH AF: 0.206

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

GnomAD4 genome AF: 0.249 AC: 37838 AN: 152110 Hom.: 5139 Cov.: 32 AF XY: 0.250 AC XY: 18572 AN XY: 74368

Gnomad4 AFR AF: 0.364

Gnomad4 AMR AF: 0.228

Gnomad4 ASJ AF: 0.231

Gnomad4 EAS AF: 0.227

Gnomad4 SAS AF: 0.169

Gnomad4 FIN AF: 0.239

Gnomad4 NFE AF: 0.195

Gnomad4 OTH AF: 0.203

Alfa AF: 0.213 Hom.: 552

Bravo AF: 0.253

Asia WGS AF: 0.189 AC: 660 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	3.1
DANN	Benign	0.66

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: rs914189; hg19: chr21-43710909;