rs225374

Variant names:

• chr21-42251523-C-G
• rs225374
• NM_016818.3:c.287-19547C>G

Your query was ambiguous. Multiple possible variants found:

• chr21-42251523-C-G
• chr21-42251523-C-T

Variant summary

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

The NM_016818.3(ABCG1):​c.287-19547C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.407 in 151,734 control chromosomes in the GnomAD database, including 12,807 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 0.41 (12807 hom., cov: 32)
• Consequence: ABCG1 NM_016818.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.96
• Publications: 5 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 (EAS) allele frequency at 95% confidence interval = 0.569 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ABCG1	NM_016818.3	c.287-19547C>G		intron_variant	Intron 2 of 14	ENST00000398449.8	NP_058198.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ABCG1	ENST00000398449.8	c.287-19547C>G		intron_variant	Intron 2 of 14	1	NM_016818.3	ENSP00000381467.3

Frequencies

GnomAD3 genomes AF: 0.407 AC: 61757 AN: 151616 Hom.: 12797 Cov.: 32

Gnomad AFR AF: 0.378

Gnomad AMI AF: 0.262

Gnomad AMR AF: 0.439

Gnomad ASJ AF: 0.428

Gnomad EAS AF: 0.586

Gnomad SAS AF: 0.518

Gnomad FIN AF: 0.366

Gnomad MID AF: 0.379

Gnomad NFE AF: 0.403

Gnomad OTH AF: 0.419

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

GnomAD4 genome AF: 0.407 AC: 61810 AN: 151734 Hom.: 12807 Cov.: 32 AF XY: 0.410 AC XY: 30408 AN XY: 74146

African (AFR) AF: 0.379 AC: 15660 AN: 41346

American (AMR) AF: 0.439 AC: 6692 AN: 15230

Ashkenazi Jewish (ASJ) AF: 0.428 AC: 1481 AN: 3464

East Asian (EAS) AF: 0.586 AC: 3017 AN: 5148

South Asian (SAS) AF: 0.518 AC: 2496 AN: 4820

European-Finnish (FIN) AF: 0.366 AC: 3860 AN: 10534

Middle Eastern (MID) AF: 0.377 AC: 110 AN: 292

European-Non Finnish (NFE) AF: 0.403 AC: 27380 AN: 67882

Other (OTH) AF: 0.416 AC: 876 AN: 2108

Alfa AF: 0.228 Hom.: 462

Bravo AF: 0.413

Asia WGS AF: 0.556 AC: 1932 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	0.10
DANN	Benign	0.46
PhyloP100		-2.0
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: rs225374; hg19: chr21-43671633;