21-42230277-A-G

Variant names:

• chr21-42230277-A-G
• rs3787968
• NM_016818.3:c.286+4363A>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.286+4363A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.517 in 152,112 control chromosomes in the GnomAD database, including 21,539 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 0.52 (21539 hom., cov: 33)
• Consequence: ABCG1 NM_016818.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.03
• Publications: 2 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=-0.52).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.7 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ABCG1	NM_016818.3	MANE Select	c.286+4363A>G		intron	N/A	NP_058198.2
	ABCG1	NM_004915.4		c.286+4363A>G		intron	N/A	NP_004906.3
	ABCG1	NM_207174.1		c.319+4363A>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+4363A>G		intron	N/A	ENSP00000381467.3
	ABCG1	ENST00000361802.7	TSL:1	c.286+4363A>G		intron	N/A	ENSP00000354995.2
	ABCG1	ENST00000343687.7	TSL:1	c.319+4363A>G		intron	N/A	ENSP00000339744.3

Frequencies

GnomAD3 genomes AF: 0.516 AC: 78489 AN: 151994 Hom.: 21511 Cov.: 33

Gnomad AFR AF: 0.707

Gnomad AMI AF: 0.359

Gnomad AMR AF: 0.468

Gnomad ASJ AF: 0.587

Gnomad EAS AF: 0.298

Gnomad SAS AF: 0.398

Gnomad FIN AF: 0.350

Gnomad MID AF: 0.557

Gnomad NFE AF: 0.460

Gnomad OTH AF: 0.525

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

GnomAD4 genome AF: 0.517 AC: 78568 AN: 152112 Hom.: 21539 Cov.: 33 AF XY: 0.507 AC XY: 37670 AN XY: 74366

African (AFR) AF: 0.707 AC: 29336 AN: 41490

American (AMR) AF: 0.468 AC: 7167 AN: 15302

Ashkenazi Jewish (ASJ) AF: 0.587 AC: 2038 AN: 3470

East Asian (EAS) AF: 0.297 AC: 1537 AN: 5174

South Asian (SAS) AF: 0.397 AC: 1918 AN: 4828

European-Finnish (FIN) AF: 0.350 AC: 3702 AN: 10570

Middle Eastern (MID) AF: 0.571 AC: 168 AN: 294

European-Non Finnish (NFE) AF: 0.460 AC: 31275 AN: 67964

Other (OTH) AF: 0.521 AC: 1101 AN: 2112

Alfa AF: 0.479 Hom.: 29642

Bravo AF: 0.533

Asia WGS AF: 0.348 AC: 1214 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.52
CADD	Benign	13
DANN	Benign	0.71
PhyloP100		1.0
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: rs3787968; hg19: chr21-43650387;