ENST00000398457.6:c.-464A>C

Variant names:

• chr21-42199485-A-C
• rs1893590
• ENST00000398457.6:c.-464A>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000398457.6(ABCG1):​c.-464A>C variant causes a upstream gene change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.353 in 152,126 control chromosomes in the GnomAD database, including 10,139 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 0.35 (10139 hom., cov: 33)
• Consequence: ABCG1 ENST00000398457.6 upstream_gene
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0310
• Publications: 22 publications found

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

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.47 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ABCG1	NM_207627.2	c.-464A>C		upstream_gene_variant			NP_997510.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ABCG1	ENST00000398457.6	c.-464A>C		upstream_gene_variant		1		ENSP00000381475.2

Frequencies

GnomAD3 genomes AF: 0.352 AC: 53582 AN: 152008 Hom.: 10128 Cov.: 33

Gnomad AFR AF: 0.475

Gnomad AMI AF: 0.287

Gnomad AMR AF: 0.362

Gnomad ASJ AF: 0.366

Gnomad EAS AF: 0.455

Gnomad SAS AF: 0.357

Gnomad FIN AF: 0.364

Gnomad MID AF: 0.360

Gnomad NFE AF: 0.267

Gnomad OTH AF: 0.326

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

GnomAD4 genome AF: 0.353 AC: 53643 AN: 152126 Hom.: 10139 Cov.: 33 AF XY: 0.357 AC XY: 26556 AN XY: 74356

African (AFR) AF: 0.476 AC: 19729 AN: 41488

American (AMR) AF: 0.363 AC: 5547 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.366 AC: 1268 AN: 3468

East Asian (EAS) AF: 0.455 AC: 2358 AN: 5178

South Asian (SAS) AF: 0.356 AC: 1718 AN: 4828

European-Finnish (FIN) AF: 0.364 AC: 3846 AN: 10564

Middle Eastern (MID) AF: 0.370 AC: 108 AN: 292

European-Non Finnish (NFE) AF: 0.267 AC: 18120 AN: 67992

Other (OTH) AF: 0.325 AC: 688 AN: 2114

Alfa AF: 0.297 Hom.: 13293

Bravo AF: 0.357

Asia WGS AF: 0.406 AC: 1415 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	1.2
DANN	Benign	0.57
PhyloP100		-0.031
PromoterAI		0.0022	Neutral

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs1893590; hg19: chr21-43619595;