NM_016818.3:c.1773-252G>A

Variant names:

• chr21-42295912-G-A
• rs3788010
• NM_016818.3:c.1773-252G>A

Variant summary

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

The NM_016818.3(ABCG1):​c.1773-252G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.498 in 151,990 control chromosomes in the GnomAD database, including 20,545 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 0.50 (20545 hom., cov: 32)
• Consequence: ABCG1 NM_016818.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.14
• Publications: 14 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=-0.92).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.585 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.1773-252G>A		intron	N/A	NP_058198.2
	ABCG1	NM_004915.4		c.1809-252G>A		intron	N/A	NP_004906.3
	ABCG1	NM_207174.1		c.1806-252G>A		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.1773-252G>A		intron	N/A	ENSP00000381467.3	P45844-4
	ABCG1	ENST00000398437.1	TSL:1	c.2247-252G>A		intron	N/A	ENSP00000381464.1	E9PGV9
	ABCG1	ENST00000361802.7	TSL:1	c.1809-252G>A		intron	N/A	ENSP00000354995.2	P45844-1

Frequencies

GnomAD3 genomes AF: 0.498 AC: 75647 AN: 151872 Hom.: 20546 Cov.: 32

Gnomad AFR AF: 0.264

Gnomad AMI AF: 0.535

Gnomad AMR AF: 0.555

Gnomad ASJ AF: 0.597

Gnomad EAS AF: 0.531

Gnomad SAS AF: 0.510

Gnomad FIN AF: 0.686

Gnomad MID AF: 0.465

Gnomad NFE AF: 0.590

Gnomad OTH AF: 0.498

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

GnomAD4 genome AF: 0.498 AC: 75670 AN: 151990 Hom.: 20545 Cov.: 32 AF XY: 0.505 AC XY: 37517 AN XY: 74280

African (AFR) AF: 0.264 AC: 10949 AN: 41438

American (AMR) AF: 0.554 AC: 8464 AN: 15268

Ashkenazi Jewish (ASJ) AF: 0.597 AC: 2071 AN: 3470

East Asian (EAS) AF: 0.531 AC: 2744 AN: 5170

South Asian (SAS) AF: 0.511 AC: 2455 AN: 4806

European-Finnish (FIN) AF: 0.686 AC: 7242 AN: 10562

Middle Eastern (MID) AF: 0.466 AC: 136 AN: 292

European-Non Finnish (NFE) AF: 0.590 AC: 40080 AN: 67962

Other (OTH) AF: 0.493 AC: 1041 AN: 2110

Alfa AF: 0.549 Hom.: 45607

Bravo AF: 0.481

Asia WGS AF: 0.493 AC: 1715 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.20
DANN	Benign	0.62
PhyloP100		-1.1
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: rs3788010; hg19: chr21-43716022;