rs13284054

Variant names:

• chr9-104906792-T-C
• rs13284054
• NM_005502.4:c.-92-3021A>G

Variant summary

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

The NM_005502.4(ABCA1):​c.-92-3021A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.123 in 150,430 control chromosomes in the GnomAD database, including 1,239 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 0.12 (1239 hom., cov: 30)
• Consequence: ABCA1 NM_005502.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.434
• Publications: 12 publications found

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]

ABCA1 Gene-Disease associations (from GenCC):

• hypoalphalipoproteinemia, primary, 1

  Inheritance: AD Classification: DEFINITIVE, LIMITED Submitted by: Ambry Genetics, Labcorp Genetics (formerly Invitae)
• Tangier disease

  Inheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Labcorp Genetics (formerly Invitae), G2P, Orphanet
• apolipoprotein A-I deficiency

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ENSG00000306712 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.65).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.148 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ABCA1	NM_005502.4	c.-92-3021A>G		intron_variant	Intron 1 of 49	ENST00000374736.8	NP_005493.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ABCA1	ENST00000374736.8	c.-92-3021A>G		intron_variant	Intron 1 of 49	1	NM_005502.4	ENSP00000363868.3

Frequencies

GnomAD3 genomes AF: 0.123 AC: 18528 AN: 150356 Hom.: 1238 Cov.: 30

Gnomad AFR AF: 0.150

Gnomad AMI AF: 0.145

Gnomad AMR AF: 0.110

Gnomad ASJ AF: 0.107

Gnomad EAS AF: 0.0587

Gnomad SAS AF: 0.0877

Gnomad FIN AF: 0.0922

Gnomad MID AF: 0.182

Gnomad NFE AF: 0.122

Gnomad OTH AF: 0.136

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

GnomAD4 genome AF: 0.123 AC: 18543 AN: 150430 Hom.: 1239 Cov.: 30 AF XY: 0.120 AC XY: 8797 AN XY: 73358

African (AFR) AF: 0.151 AC: 6150 AN: 40808

American (AMR) AF: 0.110 AC: 1660 AN: 15126

Ashkenazi Jewish (ASJ) AF: 0.107 AC: 372 AN: 3464

East Asian (EAS) AF: 0.0588 AC: 302 AN: 5132

South Asian (SAS) AF: 0.0873 AC: 413 AN: 4732

European-Finnish (FIN) AF: 0.0922 AC: 939 AN: 10182

Middle Eastern (MID) AF: 0.168 AC: 48 AN: 286

European-Non Finnish (NFE) AF: 0.122 AC: 8245 AN: 67714

Other (OTH) AF: 0.136 AC: 282 AN: 2074

Alfa AF: 0.124 Hom.: 3124

Bravo AF: 0.127

Asia WGS AF: 0.0970 AC: 337 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.65
CADD	Benign	13
DANN	Benign	0.78
PhyloP100		0.43
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: rs13284054; hg19: chr9-107669073;