21-42296791-A-G

Position:

• chr21-42296791-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.*399A>G variant causes a 3 prime UTR 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 NM_016818.3 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.104

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=-0.92).
• 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/exons	MANE	Protein	UniProt
ABCG1	NM_016818.3	c.*399A>G		3_prime_UTR_variant	15/15	ENST00000398449.8	NP_058198.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ABCG1	ENST00000398449.8	c.*399A>G		3_prime_UTR_variant	15/15	1	NM_016818.3	ENSP00000381467	P1

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

Gnomad4 AFR exome AF: 0.632

Gnomad4 AMR exome AF: 0.567

Gnomad4 ASJ exome AF: 0.594

Gnomad4 EAS exome AF: 0.544

Gnomad4 SAS exome AF: 0.515

Gnomad4 FIN exome AF: 0.628

Gnomad4 NFE exome AF: 0.541

Gnomad4 OTH exome AF: 0.556

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

Gnomad4 AFR AF: 0.643

Gnomad4 AMR AF: 0.586

Gnomad4 ASJ AF: 0.604

Gnomad4 EAS AF: 0.539

Gnomad4 SAS AF: 0.556

Gnomad4 FIN AF: 0.661

Gnomad4 NFE AF: 0.570

Gnomad4 OTH AF: 0.573

Alfa AF: 0.562 Hom.: 24531

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

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: rs1044317; hg19: chr21-43716901;