rs914189

Variant names:

• chr21-42290799-C-G
• rs914189
• NM_016818.3:c.1394-293C>G

Variant summary

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

The NM_016818.3(ABCG1):​c.1394-293C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.249 in 152,110 control chromosomes in the GnomAD database, including 5,139 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 0.25 (5139 hom., cov: 32)
• Consequence: ABCG1 NM_016818.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0300
• Publications: 15 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=-0.83).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.359 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_016818.3. 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_016818.3	MANE Select	c.1394-293C>G		intron	N/A	NP_058198.2
	ABCG1	NM_004915.4		c.1430-293C>G		intron	N/A	NP_004906.3
	ABCG1	NM_207174.1		c.1427-293C>G		intron	N/A	NP_997057.1	P45844-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ABCG1	ENST00000398449.8	TSL:1 MANE Select	c.1394-293C>G		intron	N/A	ENSP00000381467.3	P45844-4
	ABCG1	ENST00000398437.1	TSL:1	c.1868-293C>G		intron	N/A	ENSP00000381464.1	E9PGV9
	ABCG1	ENST00000361802.7	TSL:1	c.1430-293C>G		intron	N/A	ENSP00000354995.2	P45844-1

Frequencies

GnomAD3 genomes AF: 0.249 AC: 37775 AN: 151992 Hom.: 5122 Cov.: 32

Gnomad AFR AF: 0.364

Gnomad AMI AF: 0.183

Gnomad AMR AF: 0.228

Gnomad ASJ AF: 0.231

Gnomad EAS AF: 0.227

Gnomad SAS AF: 0.167

Gnomad FIN AF: 0.239

Gnomad MID AF: 0.212

Gnomad NFE AF: 0.195

Gnomad OTH AF: 0.206

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

GnomAD4 genome AF: 0.249 AC: 37838 AN: 152110 Hom.: 5139 Cov.: 32 AF XY: 0.250 AC XY: 18572 AN XY: 74368

African (AFR) AF: 0.364 AC: 15109 AN: 41472

American (AMR) AF: 0.228 AC: 3491 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.231 AC: 800 AN: 3466

East Asian (EAS) AF: 0.227 AC: 1174 AN: 5178

South Asian (SAS) AF: 0.169 AC: 815 AN: 4818

European-Finnish (FIN) AF: 0.239 AC: 2538 AN: 10598

Middle Eastern (MID) AF: 0.207 AC: 61 AN: 294

European-Non Finnish (NFE) AF: 0.195 AC: 13254 AN: 67972

Other (OTH) AF: 0.203 AC: 429 AN: 2112

Alfa AF: 0.213 Hom.: 552

Bravo AF: 0.253

Asia WGS AF: 0.189 AC: 660 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	3.1
DANN	Benign	0.66
PhyloP100		0.030
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: rs914189; hg19: chr21-43710909;