21-42296791-A-G

Variant names:

• chr21-42296791-A-G
• rs1044317
• ENST00000462050.5:n.2584A>G

Variant summary

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

The ENST00000462050.5(ABCG1):​n.2584A>G variant causes a non coding transcript exon change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.581 in 231,564 control chromosomes in the GnomAD database, including 39,306 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 0.60 (27171 hom., cov: 32)
  • Exomes 𝑓: 0.55 (12135 hom.)
• Consequence: ABCG1 ENST00000462050.5 non_coding_transcript_exon
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.104
• Publications: 14 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=-0.92).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.636 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ABCG1	NM_016818.3	c.*399A>G		3_prime_UTR_variant	Exon 15 of 15	ENST00000398449.8	NP_058198.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ABCG1	ENST00000398449.8	c.*399A>G		3_prime_UTR_variant	Exon 15 of 15	1	NM_016818.3	ENSP00000381467.3
ABCG1	ENST00000398437.1	c.*399A>G		3_prime_UTR_variant	Exon 16 of 16	1		ENSP00000381464.1

Frequencies

GnomAD3 genomes AF: 0.597 AC: 90643 AN: 151900 Hom.: 27143 Cov.: 32

Gnomad AFR AF: 0.642

Gnomad AMI AF: 0.533

Gnomad AMR AF: 0.586

Gnomad ASJ AF: 0.604

Gnomad EAS AF: 0.539

Gnomad SAS AF: 0.556

Gnomad FIN AF: 0.661

Gnomad MID AF: 0.532

Gnomad NFE AF: 0.570

Gnomad OTH AF: 0.578

GnomAD4 exome AF: 0.551 AC: 43853 AN: 79546 Hom.: 12135 Cov.: 0 AF XY: 0.550 AC XY: 22586 AN XY: 41096

African (AFR) AF: 0.632 AC: 2308 AN: 3650

American (AMR) AF: 0.567 AC: 2701 AN: 4766

Ashkenazi Jewish (ASJ) AF: 0.594 AC: 1355 AN: 2280

East Asian (EAS) AF: 0.544 AC: 3488 AN: 6406

South Asian (SAS) AF: 0.515 AC: 3250 AN: 6310

European-Finnish (FIN) AF: 0.628 AC: 2239 AN: 3568

Middle Eastern (MID) AF: 0.516 AC: 159 AN: 308

European-Non Finnish (NFE) AF: 0.541 AC: 25929 AN: 47902

Other (OTH) AF: 0.556 AC: 2424 AN: 4356

GnomAD4 genome AF: 0.597 AC: 90727 AN: 152018 Hom.: 27171 Cov.: 32 AF XY: 0.601 AC XY: 44639 AN XY: 74302

African (AFR) AF: 0.643 AC: 26649 AN: 41454

American (AMR) AF: 0.586 AC: 8950 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.604 AC: 2096 AN: 3470

East Asian (EAS) AF: 0.539 AC: 2783 AN: 5168

South Asian (SAS) AF: 0.556 AC: 2680 AN: 4818

European-Finnish (FIN) AF: 0.661 AC: 6983 AN: 10558

Middle Eastern (MID) AF: 0.527 AC: 155 AN: 294

European-Non Finnish (NFE) AF: 0.570 AC: 38740 AN: 67966

Other (OTH) AF: 0.573 AC: 1207 AN: 2106

Alfa AF: 0.570 Hom.: 45728

Bravo AF: 0.594

Asia WGS AF: 0.538 AC: 1871 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	2.2
DANN	Benign	0.27
PhyloP100		-0.10
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: rs1044317; hg19: chr21-43716901;