rs225390

Positions:

• chr21-42264475-A-G

Variant summary

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

The NM_016818.3(ABCG1):​c.287-6595A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.703 in 151,690 control chromosomes in the GnomAD database, including 38,257 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 0.70 (38257 hom., cov: 31)
• Consequence: ABCG1 NM_016818.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.22

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=-1.01).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.842 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ABCG1	NM_016818.3	c.287-6595A>G		intron_variant		ENST00000398449.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ABCG1	ENST00000398449.8	c.287-6595A>G		intron_variant		1	NM_016818.3	P1

Frequencies

GnomAD3 genomes AF: 0.703 AC: 106528 AN: 151572 Hom.: 38206 Cov.: 31

Gnomad AFR AF: 0.850

Gnomad AMI AF: 0.709

Gnomad AMR AF: 0.670

Gnomad ASJ AF: 0.644

Gnomad EAS AF: 0.474

Gnomad SAS AF: 0.535

Gnomad FIN AF: 0.560

Gnomad MID AF: 0.753

Gnomad NFE AF: 0.675

Gnomad OTH AF: 0.699

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

GnomAD4 genome AF: 0.703 AC: 106640 AN: 151690 Hom.: 38257 Cov.: 31 AF XY: 0.689 AC XY: 51091 AN XY: 74142

Gnomad4 AFR AF: 0.850

Gnomad4 AMR AF: 0.671

Gnomad4 ASJ AF: 0.644

Gnomad4 EAS AF: 0.474

Gnomad4 SAS AF: 0.535

Gnomad4 FIN AF: 0.560

Gnomad4 NFE AF: 0.675

Gnomad4 OTH AF: 0.702

Alfa AF: 0.689 Hom.: 4530

Bravo AF: 0.720

Asia WGS AF: 0.563 AC: 1963 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.85
DANN	Benign	0.27

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: rs225390; hg19: chr21-43684585;