9-104839260-G-A

Variant names:

• chr9-104839260-G-A
• rs2472386
• NM_005502.4:c.1054+1019C>T

Variant summary

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

The NM_005502.4(ABCA1):​c.1054+1019C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.471 in 151,956 control chromosomes in the GnomAD database, including 19,340 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 0.47 (19340 hom., cov: 32)
• Consequence: ABCA1 NM_005502.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.346
• Publications: 17 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

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.8).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.774 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_005502.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ABCA1	NM_005502.4	MANE Select	c.1054+1019C>T		intron	N/A	NP_005493.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ABCA1	ENST00000374736.8	TSL:1 MANE Select	c.1054+1019C>T		intron	N/A	ENSP00000363868.3
	ABCA1	ENST00000678995.1		c.1054+1019C>T		intron	N/A	ENSP00000504612.1

Frequencies

GnomAD3 genomes AF: 0.471 AC: 71489 AN: 151838 Hom.: 19303 Cov.: 32

Gnomad AFR AF: 0.722

Gnomad AMI AF: 0.475

Gnomad AMR AF: 0.440

Gnomad ASJ AF: 0.382

Gnomad EAS AF: 0.795

Gnomad SAS AF: 0.450

Gnomad FIN AF: 0.272

Gnomad MID AF: 0.484

Gnomad NFE AF: 0.337

Gnomad OTH AF: 0.465

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

GnomAD4 genome AF: 0.471 AC: 71582 AN: 151956 Hom.: 19340 Cov.: 32 AF XY: 0.469 AC XY: 34827 AN XY: 74246

African (AFR) AF: 0.723 AC: 29943 AN: 41442

American (AMR) AF: 0.440 AC: 6719 AN: 15268

Ashkenazi Jewish (ASJ) AF: 0.382 AC: 1326 AN: 3470

East Asian (EAS) AF: 0.794 AC: 4097 AN: 5160

South Asian (SAS) AF: 0.449 AC: 2161 AN: 4810

European-Finnish (FIN) AF: 0.272 AC: 2866 AN: 10530

Middle Eastern (MID) AF: 0.476 AC: 139 AN: 292

European-Non Finnish (NFE) AF: 0.337 AC: 22905 AN: 67960

Other (OTH) AF: 0.470 AC: 993 AN: 2112

Alfa AF: 0.378 Hom.: 6183

Bravo AF: 0.498

Asia WGS AF: 0.620 AC: 2151 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	3.9
DANN	Benign	0.48
PhyloP100		0.35
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: rs2472386; hg19: chr9-107601541;