chr21-42286991-C-G

Variant names:

• chr21-42286991-C-G
• rs425215
• NM_016818.3:c.974-898C>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.974-898C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.634 in 151,976 control chromosomes in the GnomAD database, including 30,968 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 0.63 (30968 hom., cov: 31)
• Consequence: ABCG1 NM_016818.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.603
• Publications: 16 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=-0.9).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.658 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ABCG1	NM_016818.3	c.974-898C>G		intron_variant	Intron 8 of 14	ENST00000398449.8	NP_058198.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ABCG1	ENST00000398449.8	c.974-898C>G		intron_variant	Intron 8 of 14	1	NM_016818.3	ENSP00000381467.3
ABCG1	ENST00000398437.1	c.1412-898C>G		intron_variant	Intron 9 of 15	1		ENSP00000381464.1

Frequencies

GnomAD3 genomes AF: 0.634 AC: 96231 AN: 151858 Hom.: 30943 Cov.: 31

Gnomad AFR AF: 0.665

Gnomad AMI AF: 0.734

Gnomad AMR AF: 0.658

Gnomad ASJ AF: 0.648

Gnomad EAS AF: 0.305

Gnomad SAS AF: 0.536

Gnomad FIN AF: 0.686

Gnomad MID AF: 0.592

Gnomad NFE AF: 0.631

Gnomad OTH AF: 0.634

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

GnomAD4 genome AF: 0.634 AC: 96312 AN: 151976 Hom.: 30968 Cov.: 31 AF XY: 0.635 AC XY: 47150 AN XY: 74278

African (AFR) AF: 0.665 AC: 27543 AN: 41434

American (AMR) AF: 0.658 AC: 10056 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.648 AC: 2250 AN: 3470

East Asian (EAS) AF: 0.305 AC: 1568 AN: 5138

South Asian (SAS) AF: 0.536 AC: 2574 AN: 4804

European-Finnish (FIN) AF: 0.686 AC: 7261 AN: 10578

Middle Eastern (MID) AF: 0.595 AC: 175 AN: 294

European-Non Finnish (NFE) AF: 0.631 AC: 42887 AN: 67962

Other (OTH) AF: 0.632 AC: 1330 AN: 2106

Alfa AF: 0.621 Hom.: 15971

Bravo AF: 0.634

Asia WGS AF: 0.471 AC: 1639 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.82
DANN	Benign	0.69
PhyloP100		-0.60
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: rs425215; hg19: chr21-43707101;