rs2234715

Positions:

• chr21-42218745-A-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000398457.6(ABCG1):​c.49-6926A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0702 in 152,128 control chromosomes in the GnomAD database, including 502 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 0.070 (502 hom., cov: 32)
• Consequence: ABCG1 ENST00000398457.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.21

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]

LOC105372814 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.207 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
LOC105372814	XR_937748.4	n.121+1405T>C		intron_variant, non_coding_transcript_variant
ABCG1	NM_207627.2	c.49-6926A>G		intron_variant
ABCG1	NM_207628.1	c.-24-6926A>G		intron_variant
ABCG1	NM_207629.2	c.33+2557A>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ABCG1	ENST00000347800.6	c.33+2557A>G		intron_variant		1
ABCG1	ENST00000398457.6	c.49-6926A>G		intron_variant		1
ABCG1	ENST00000462050.5	n.227-6926A>G		intron_variant, non_coding_transcript_variant		1

Frequencies

GnomAD3 genomes AF: 0.0702 AC: 10678 AN: 152010 Hom.: 502 Cov.: 32

Gnomad AFR AF: 0.0168

Gnomad AMI AF: 0.0373

Gnomad AMR AF: 0.0908

Gnomad ASJ AF: 0.145

Gnomad EAS AF: 0.218

Gnomad SAS AF: 0.164

Gnomad FIN AF: 0.0759

Gnomad MID AF: 0.0633

Gnomad NFE AF: 0.0759

Gnomad OTH AF: 0.0759

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

GnomAD4 genome AF: 0.0702 AC: 10673 AN: 152128 Hom.: 502 Cov.: 32 AF XY: 0.0745 AC XY: 5542 AN XY: 74364

Gnomad4 AFR AF: 0.0168

Gnomad4 AMR AF: 0.0908

Gnomad4 ASJ AF: 0.145

Gnomad4 EAS AF: 0.217

Gnomad4 SAS AF: 0.164

Gnomad4 FIN AF: 0.0759

Gnomad4 NFE AF: 0.0759

Gnomad4 OTH AF: 0.0751

Alfa AF: 0.0797 Hom.: 434

Bravo AF: 0.0658

Asia WGS AF: 0.155 AC: 538 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	9.1
DANN	Benign	0.55

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs2234715; hg19: chr21-43638855;