21-42230346-A-G

Variant names:

• chr21-42230346-A-G
• rs170444
• NM_016818.3:c.286+4432A>G

Variant summary

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

The ENST00000398449.8(ABCG1):​c.286+4432A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.997 in 152,350 control chromosomes in the GnomAD database, including 75,711 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 1.0 (75711 hom., cov: 33)
• Consequence: ABCG1 ENST00000398449.8 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.263
• Publications: 3 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=-0.79).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.993 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000398449.8. 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.286+4432A>G		intron	N/A	NP_058198.2
	ABCG1	NM_004915.4		c.286+4432A>G		intron	N/A	NP_004906.3
	ABCG1	NM_207174.1		c.319+4432A>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.286+4432A>G		intron	N/A	ENSP00000381467.3
	ABCG1	ENST00000361802.7	TSL:1	c.286+4432A>G		intron	N/A	ENSP00000354995.2
	ABCG1	ENST00000343687.7	TSL:1	c.319+4432A>G		intron	N/A	ENSP00000339744.3

Frequencies

GnomAD3 genomes AF: 0.997 AC: 151756 AN: 152232 Hom.: 75651 Cov.: 33

Gnomad AFR AF: 1.00

Gnomad AMI AF: 1.00

Gnomad AMR AF: 0.989

Gnomad ASJ AF: 1.00

Gnomad EAS AF: 0.952

Gnomad SAS AF: 0.997

Gnomad FIN AF: 1.00

Gnomad MID AF: 0.997

Gnomad NFE AF: 1.00

Gnomad OTH AF: 0.998

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

GnomAD4 genome AF: 0.997 AC: 151875 AN: 152350 Hom.: 75711 Cov.: 33 AF XY: 0.996 AC XY: 74203 AN XY: 74488

African (AFR) AF: 1.00 AC: 41574 AN: 41582

American (AMR) AF: 0.989 AC: 15137 AN: 15310

Ashkenazi Jewish (ASJ) AF: 1.00 AC: 3472 AN: 3472

East Asian (EAS) AF: 0.952 AC: 4939 AN: 5186

South Asian (SAS) AF: 0.997 AC: 4806 AN: 4820

European-Finnish (FIN) AF: 1.00 AC: 10620 AN: 10620

Middle Eastern (MID) AF: 0.997 AC: 293 AN: 294

European-Non Finnish (NFE) AF: 1.00 AC: 68012 AN: 68040

Other (OTH) AF: 0.998 AC: 2110 AN: 2114

Alfa AF: 0.998 Hom.: 39835

Bravo AF: 0.996

Asia WGS AF: 0.976 AC: 3394 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
CADD	Benign	4.5
DANN	Benign	0.50
PhyloP100		0.26
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: rs170444; hg19: chr21-43650456;