rs57137919

Variant names:

• chr21-42218908-G-A
• rs57137919
• ENST00000398457.6:c.49-6763G>A

Variant summary

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

The ENST00000398457.6(ABCG1):​c.49-6763G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.138 in 152,162 control chromosomes in the GnomAD database, including 1,711 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 0.14 (1711 hom., cov: 32)
• Consequence: ABCG1 ENST00000398457.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.251
• Publications: 19 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]

LOC105372814 (HGNC:):

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.228 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ABCG1	NM_016818.3	c.-355G>A		upstream_gene_variant		ENST00000398449.8	NP_058198.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ABCG1	ENST00000398449.8	c.-355G>A		upstream_gene_variant		1	NM_016818.3	ENSP00000381467.3

Frequencies

GnomAD3 genomes AF: 0.138 AC: 20922 AN: 152054 Hom.: 1708 Cov.: 32

Gnomad AFR AF: 0.0651

Gnomad AMI AF: 0.208

Gnomad AMR AF: 0.190

Gnomad ASJ AF: 0.185

Gnomad EAS AF: 0.239

Gnomad SAS AF: 0.155

Gnomad FIN AF: 0.264

Gnomad MID AF: 0.171

Gnomad NFE AF: 0.138

Gnomad OTH AF: 0.133

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

GnomAD4 genome AF: 0.138 AC: 20924 AN: 152162 Hom.: 1711 Cov.: 32 AF XY: 0.143 AC XY: 10642 AN XY: 74374

African (AFR) AF: 0.0649 AC: 2697 AN: 41536

American (AMR) AF: 0.191 AC: 2913 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.185 AC: 643 AN: 3472

East Asian (EAS) AF: 0.239 AC: 1232 AN: 5160

South Asian (SAS) AF: 0.155 AC: 747 AN: 4824

European-Finnish (FIN) AF: 0.264 AC: 2794 AN: 10600

Middle Eastern (MID) AF: 0.167 AC: 49 AN: 294

European-Non Finnish (NFE) AF: 0.138 AC: 9383 AN: 67964

Other (OTH) AF: 0.131 AC: 277 AN: 2112

Alfa AF: 0.135 Hom.: 190

Bravo AF: 0.131

Asia WGS AF: 0.194 AC: 676 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	7.2
DANN	Benign	0.90
PhyloP100		0.25
PromoterAI		0.0050	Neutral
Mutation Taster		=100/0	polymorphism (auto)

Splicing

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

Other links and lift over

dbSNP: rs57137919; hg19: chr21-43639018;