rs2234715

Variant names:

• chr21-42218745-A-G
• rs2234715
• ENST00000398457.6:c.49-6926A>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.49-6926A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0702 in 152,128 control chromosomes in the GnomAD database, including 502 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 0.070 (502 hom., cov: 32)
• Consequence: ABCG1 NM_207627.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.21
• Publications: 4 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=-0.84).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.207 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.49-6926A>G		intron	N/A	NP_997510.1	P45844-3
	ABCG1	NM_207629.2		c.33+2557A>G		intron	N/A	NP_997512.1	P45844-5
	ABCG1	NM_207628.1		c.-24-6926A>G		intron	N/A	NP_997511.1	P45844-7

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ABCG1	ENST00000398457.6	TSL:1	c.49-6926A>G		intron	N/A	ENSP00000381475.2	P45844-3
	ABCG1	ENST00000347800.6	TSL:1	c.33+2557A>G		intron	N/A	ENSP00000291524.4	P45844-5
	ABCG1	ENST00000462050.5	TSL:1	n.227-6926A>G		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.0702 AC: 10678 AN: 152010 Hom.: 502 Cov.: 32

Gnomad AFR AF: 0.0168

Gnomad AMI AF: 0.0373

Gnomad AMR AF: 0.0908

Gnomad ASJ AF: 0.145

Gnomad EAS AF: 0.218

Gnomad SAS AF: 0.164

Gnomad FIN AF: 0.0759

Gnomad MID AF: 0.0633

Gnomad NFE AF: 0.0759

Gnomad OTH AF: 0.0759

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

GnomAD4 genome AF: 0.0702 AC: 10673 AN: 152128 Hom.: 502 Cov.: 32 AF XY: 0.0745 AC XY: 5542 AN XY: 74364

African (AFR) AF: 0.0168 AC: 697 AN: 41524

American (AMR) AF: 0.0908 AC: 1389 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.145 AC: 502 AN: 3470

East Asian (EAS) AF: 0.217 AC: 1119 AN: 5146

South Asian (SAS) AF: 0.164 AC: 790 AN: 4818

European-Finnish (FIN) AF: 0.0759 AC: 804 AN: 10588

Middle Eastern (MID) AF: 0.0646 AC: 19 AN: 294

European-Non Finnish (NFE) AF: 0.0759 AC: 5160 AN: 67970

Other (OTH) AF: 0.0751 AC: 159 AN: 2116

Alfa AF: 0.0770 Hom.: 569

Bravo AF: 0.0658

Asia WGS AF: 0.155 AC: 538 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	9.1
DANN	Benign	0.55
PhyloP100		2.2
PromoterAI		-0.00030	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: rs2234715; hg19: chr21-43638855;