rs225390

Variant names:

• chr21-42264475-A-G
• rs225390
• NM_016818.3:c.287-6595A>G

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 10 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=-1.01).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.842 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_016818.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ABCG1	NM_016818.3	MANE Select	c.287-6595A>G		intron	N/A	NP_058198.2
	ABCG1	NM_004915.4		c.287-6595A>G		intron	N/A	NP_004906.3
	ABCG1	NM_207174.1		c.320-6595A>G		intron	N/A	NP_997057.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ABCG1	ENST00000398449.8	TSL:1 MANE Select	c.287-6595A>G		intron	N/A	ENSP00000381467.3
	ABCG1	ENST00000398437.1	TSL:1	c.724+4336A>G		intron	N/A	ENSP00000381464.1
	ABCG1	ENST00000361802.7	TSL:1	c.287-6595A>G		intron	N/A	ENSP00000354995.2

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

African (AFR) AF: 0.850 AC: 35130 AN: 41350

American (AMR) AF: 0.671 AC: 10243 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.644 AC: 2223 AN: 3454

East Asian (EAS) AF: 0.474 AC: 2433 AN: 5136

South Asian (SAS) AF: 0.535 AC: 2563 AN: 4788

European-Finnish (FIN) AF: 0.560 AC: 5894 AN: 10534

Middle Eastern (MID) AF: 0.752 AC: 221 AN: 294

European-Non Finnish (NFE) AF: 0.675 AC: 45803 AN: 67834

Other (OTH) AF: 0.702 AC: 1485 AN: 2116

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 v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.85
DANN	Benign	0.27
PhyloP100		-2.2
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: rs225390; hg19: chr21-43684585;