21-42199555-T-G

Variant names:

• chr21-42199555-T-G
• rs1378577
• ENST00000398457.6:c.-394T>G

Variant summary

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

The NM_207627.2(ABCG1):​c.-394T>G variant causes a upstream gene change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.331 in 152,130 control chromosomes in the GnomAD database, including 9,523 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 0.33 (9523 hom., cov: 33)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: ABCG1 NM_207627.2 upstream_gene
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.566
• Publications: 22 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=-0.91).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.499 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_207627.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ABCG1	NM_207627.2		c.-394T>G		upstream_gene	N/A	NP_997510.1	P45844-3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ABCG1	ENST00000398457.6	TSL:1	c.-394T>G		upstream_gene	N/A	ENSP00000381475.2	P45844-3

Frequencies

GnomAD3 genomes AF: 0.331 AC: 50241 AN: 152012 Hom.: 9506 Cov.: 33

Gnomad AFR AF: 0.505

Gnomad AMI AF: 0.212

Gnomad AMR AF: 0.335

Gnomad ASJ AF: 0.330

Gnomad EAS AF: 0.455

Gnomad SAS AF: 0.328

Gnomad FIN AF: 0.339

Gnomad MID AF: 0.294

Gnomad NFE AF: 0.216

Gnomad OTH AF: 0.295

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 10 Hom.: 0 AF XY: 0.00 AC XY: 0 AN XY: 8

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 2

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 6

Other (OTH) AF: 0.00 AC: 0 AN: 2

GnomAD4 genome AF: 0.331 AC: 50307 AN: 152130 Hom.: 9523 Cov.: 33 AF XY: 0.337 AC XY: 25023 AN XY: 74360

African (AFR) AF: 0.505 AC: 20929 AN: 41474

American (AMR) AF: 0.335 AC: 5129 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.330 AC: 1143 AN: 3468

East Asian (EAS) AF: 0.455 AC: 2358 AN: 5178

South Asian (SAS) AF: 0.326 AC: 1573 AN: 4822

European-Finnish (FIN) AF: 0.339 AC: 3580 AN: 10570

Middle Eastern (MID) AF: 0.306 AC: 90 AN: 294

European-Non Finnish (NFE) AF: 0.216 AC: 14690 AN: 67998

Other (OTH) AF: 0.294 AC: 622 AN: 2114

Alfa AF: 0.244 Hom.: 8455

Bravo AF: 0.336

Asia WGS AF: 0.396 AC: 1378 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	6.0
DANN	Benign	0.69
PhyloP100		0.57
PromoterAI		0.046	Neutral

Splicing

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

Other links and lift over

dbSNP: rs1378577; hg19: chr21-43619665;