chr21-42295912-G-A

Position:

• chr21-42295912-G-A

Variant summary

Our verdict is Benign. Variant got -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

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

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ABCG1	NM_016818.3	c.1773-252G>A		intron_variant		ENST00000398449.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ABCG1	ENST00000398449.8	c.1773-252G>A		intron_variant		1	NM_016818.3	P1

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

Gnomad4 AFR AF: 0.264

Gnomad4 AMR AF: 0.554

Gnomad4 ASJ AF: 0.597

Gnomad4 EAS AF: 0.531

Gnomad4 SAS AF: 0.511

Gnomad4 FIN AF: 0.686

Gnomad4 NFE AF: 0.590

Gnomad4 OTH AF: 0.493

Alfa AF: 0.566 Hom.: 31834

Bravo AF: 0.481

Asia WGS AF: 0.493 AC: 1715 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.20
DANN	Benign	0.62

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

Publications

LitVar

Other links and lift over

dbSNP: rs3788010; hg19: chr21-43716022;