rs2487054

chr9-104842441-A-Cchr9-104842441-A-Gchr9-104842441-A-T

Variant summary

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

The NM_005502.4(ABCA1):c.814-1922T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.544 in 151,934 control chromosomes in the GnomAD database, including 25,074 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 0.54 (25074 hom., cov: 31)
• Consequence: ABCA1 NM_005502.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -3.04

Genes affected

ABCA1 (HGNC:29): (ATP binding cassette subfamily A member 1) The membrane-associated 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 intracellular membranes. ABC genes are divided into seven distinct subfamilies (ABC1, MDR/TAP, MRP, ALD, OABP, GCN20, White). This protein is a member of the ABC1 subfamily. Members of the ABC1 subfamily comprise the only major ABC subfamily found exclusively in multicellular eukaryotes. With cholesterol as its substrate, this protein functions as a cholesteral efflux pump in the cellular lipid removal pathway. Mutations in both alleles of this gene cause Tangier disease and familial high-density lipoprotein (HDL) deficiency. [provided by RefSeq, Sep 2019]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.0).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.805 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ABCA1	NM_005502.4	c.814-1922T>G		intron_variant		ENST00000374736.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ABCA1	ENST00000374736.8	c.814-1922T>G		intron_variant		1	NM_005502.4	P1
ABCA1	ENST00000678995.1	c.814-1922T>G		intron_variant

Frequencies

GnomAD3 genomes AF: 0.543 AC: 82482 AN: 151816 Hom.: 25013 Cov.: 31

Gnomad AFR AF: 0.812

Gnomad AMI AF: 0.503

Gnomad AMR AF: 0.480

Gnomad ASJ AF: 0.418

Gnomad EAS AF: 0.810

Gnomad SAS AF: 0.477

Gnomad FIN AF: 0.363

Gnomad MID AF: 0.506

Gnomad NFE AF: 0.414

Gnomad OTH AF: 0.527

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

GnomAD4 genome AF: 0.544 AC: 82604 AN: 151934 Hom.: 25074 Cov.: 31 AF XY: 0.540 AC XY: 40122 AN XY: 74272

Gnomad4 AFR AF: 0.813

Gnomad4 AMR AF: 0.481

Gnomad4 ASJ AF: 0.418

Gnomad4 EAS AF: 0.809

Gnomad4 SAS AF: 0.475

Gnomad4 FIN AF: 0.363

Gnomad4 NFE AF: 0.414

Gnomad4 OTH AF: 0.533

Alfa AF: 0.449 Hom.: 8373

Bravo AF: 0.564

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
Cadd	Benign	0.15
Dann	Benign	0.46

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: rs2487054; hg19: chr9-107604722;