rs2234714

Variant names:

• chr21-42218507-G-A
• rs2234714
• ENST00000398457.6:c.49-7164G>A

Variant summary

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

The NM_207627.2(ABCG1):​c.49-7164G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.334 in 152,002 control chromosomes in the GnomAD database, including 8,938 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 (8938 hom., cov: 32)
• Consequence: ABCG1 NM_207627.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.208
• 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]

LOC105372814 (HGNC:):

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.443 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.49-7164G>A		intron	N/A	NP_997510.1	P45844-3
	ABCG1	NM_207629.2		c.33+2319G>A		intron	N/A	NP_997512.1	P45844-5
	ABCG1	NM_207628.1		c.-24-7164G>A		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.49-7164G>A		intron	N/A	ENSP00000381475.2	P45844-3
	ABCG1	ENST00000347800.6	TSL:1	c.33+2319G>A		intron	N/A	ENSP00000291524.4	P45844-5
	ABCG1	ENST00000462050.5	TSL:1	n.227-7164G>A		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.334 AC: 50773 AN: 151884 Hom.: 8921 Cov.: 32

Gnomad AFR AF: 0.411

Gnomad AMI AF: 0.318

Gnomad AMR AF: 0.356

Gnomad ASJ AF: 0.367

Gnomad EAS AF: 0.459

Gnomad SAS AF: 0.349

Gnomad FIN AF: 0.365

Gnomad MID AF: 0.332

Gnomad NFE AF: 0.267

Gnomad OTH AF: 0.312

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

GnomAD4 genome AF: 0.334 AC: 50833 AN: 152002 Hom.: 8938 Cov.: 32 AF XY: 0.340 AC XY: 25227 AN XY: 74294

African (AFR) AF: 0.411 AC: 17044 AN: 41458

American (AMR) AF: 0.356 AC: 5439 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.367 AC: 1274 AN: 3470

East Asian (EAS) AF: 0.459 AC: 2362 AN: 5148

South Asian (SAS) AF: 0.347 AC: 1674 AN: 4818

European-Finnish (FIN) AF: 0.365 AC: 3848 AN: 10552

Middle Eastern (MID) AF: 0.337 AC: 99 AN: 294

European-Non Finnish (NFE) AF: 0.267 AC: 18146 AN: 67968

Other (OTH) AF: 0.312 AC: 658 AN: 2112

Alfa AF: 0.304 Hom.: 1647

Bravo AF: 0.336

Asia WGS AF: 0.398 AC: 1385 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	5.3
DANN	Benign	0.42
PhyloP100		0.21
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: rs2234714; hg19: chr21-43638617;