rs2234714

Positions:

• chr21-42218507-G-A

Variant summary

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

The ENST00000398457.6(ABCG1):​c.49-7164G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.334 in 152,002 control chromosomes in the GnomAD database, including 8,938 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 0.33 (8938 hom., cov: 32)
• Consequence: ABCG1 ENST00000398457.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.208

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=-0.86).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.443 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
LOC105372814	XR_937748.4	n.121+1643C>T		intron_variant, non_coding_transcript_variant
ABCG1	NM_207627.2	c.49-7164G>A		intron_variant			NP_997510.1
ABCG1	NM_207628.1	c.-24-7164G>A		intron_variant			NP_997511.1
ABCG1	NM_207629.2	c.33+2319G>A		intron_variant			NP_997512.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ABCG1	ENST00000347800.6	c.33+2319G>A		intron_variant		1		ENSP00000291524
ABCG1	ENST00000398457.6	c.49-7164G>A		intron_variant		1		ENSP00000381475
ABCG1	ENST00000462050.5	n.227-7164G>A		intron_variant, non_coding_transcript_variant		1

Frequencies

GnomAD3 genomes AF: 0.334 AC: 50773 AN: 151884 Hom.: 8921 Cov.: 32

Gnomad AFR AF: 0.411

Gnomad AMI AF: 0.318

Gnomad AMR AF: 0.356

Gnomad ASJ AF: 0.367

Gnomad EAS AF: 0.459

Gnomad SAS AF: 0.349

Gnomad FIN AF: 0.365

Gnomad MID AF: 0.332

Gnomad NFE AF: 0.267

Gnomad OTH AF: 0.312

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

GnomAD4 genome AF: 0.334 AC: 50833 AN: 152002 Hom.: 8938 Cov.: 32 AF XY: 0.340 AC XY: 25227 AN XY: 74294

Gnomad4 AFR AF: 0.411

Gnomad4 AMR AF: 0.356

Gnomad4 ASJ AF: 0.367

Gnomad4 EAS AF: 0.459

Gnomad4 SAS AF: 0.347

Gnomad4 FIN AF: 0.365

Gnomad4 NFE AF: 0.267

Gnomad4 OTH AF: 0.312

Alfa AF: 0.304 Hom.: 1647

Bravo AF: 0.336

Asia WGS AF: 0.398 AC: 1385 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	5.3
DANN	Benign	0.42

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs2234714; hg19: chr21-43638617;