rs2740486

chr9-104904232-T-G

Variant summary

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

The NM_005502.4(ABCA1):c.-92-461A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.546 in 151,960 control chromosomes in the GnomAD database, including 23,918 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 0.55 (23918 hom., cov: 31)
• Consequence: ABCA1 NM_005502.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.145

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=-0.9).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.739 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ABCA1	NM_005502.4	c.-92-461A>C		intron_variant		ENST00000374736.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ABCA1	ENST00000374736.8	c.-92-461A>C		intron_variant		1	NM_005502.4	P1
ABCA1	ENST00000374733.1	c.-114-15037A>C		intron_variant		2
ABCA1	ENST00000423487.6	c.-92-461A>C		intron_variant		2
ABCA1	ENST00000678995.1	c.-92-461A>C		intron_variant

Frequencies

GnomAD3 genomes AF: 0.546 AC: 82931 AN: 151842 Hom.: 23883 Cov.: 31

Gnomad AFR AF: 0.723

Gnomad AMI AF: 0.548

Gnomad AMR AF: 0.459

Gnomad ASJ AF: 0.558

Gnomad EAS AF: 0.759

Gnomad SAS AF: 0.488

Gnomad FIN AF: 0.427

Gnomad MID AF: 0.551

Gnomad NFE AF: 0.464

Gnomad OTH AF: 0.535

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

GnomAD4 genome AF: 0.546 AC: 83014 AN: 151960 Hom.: 23918 Cov.: 31 AF XY: 0.541 AC XY: 40197 AN XY: 74308

Gnomad4 AFR AF: 0.723

Gnomad4 AMR AF: 0.459

Gnomad4 ASJ AF: 0.558

Gnomad4 EAS AF: 0.759

Gnomad4 SAS AF: 0.485

Gnomad4 FIN AF: 0.427

Gnomad4 NFE AF: 0.464

Gnomad4 OTH AF: 0.539

Alfa AF: 0.482 Hom.: 36898

Bravo AF: 0.561

Asia WGS AF: 0.633 AC: 2202 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
Cadd	Benign	1.7
Dann	Benign	0.65

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: rs2740486; hg19: chr9-107666513;