rs2482424

chr9-104903470-C-T

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_005502.4(ABCA1):c.66+144G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.134 in 870,922 control chromosomes in the GnomAD database, including 8,937 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.12 (1346 hom., cov: 32)
  • Exomes 𝑓: 0.14 (7591 hom.)
• Consequence: ABCA1 NM_005502.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.654

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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.77).
• BP6: Variant 9-104903470-C-T is Benign according to our data. Variant chr9-104903470-C-T is described in ClinVar as [Benign]. Clinvar id is 1221279.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr9-104903470-C-T is described in Lovd as [Benign].
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.222 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ABCA1	NM_005502.4	c.66+144G>A		intron_variant		ENST00000374736.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ABCA1	ENST00000374736.8	c.66+144G>A		intron_variant		1	NM_005502.4	P1
ABCA1	ENST00000374733.1	c.-114-14275G>A		intron_variant		2
ABCA1	ENST00000423487.6	c.66+144G>A		intron_variant		2
ABCA1	ENST00000678995.1	c.66+144G>A		intron_variant

Frequencies

GnomAD3 genomes AF: 0.116 AC: 17667 AN: 152086 Hom.: 1348 Cov.: 32

Gnomad AFR AF: 0.0284

Gnomad AMI AF: 0.0581

Gnomad AMR AF: 0.228

Gnomad ASJ AF: 0.0824

Gnomad EAS AF: 0.169

Gnomad SAS AF: 0.145

Gnomad FIN AF: 0.146

Gnomad MID AF: 0.0475

Gnomad NFE AF: 0.136

Gnomad OTH AF: 0.124

GnomAD4 exome AF: 0.138 AC: 98914 AN: 718718 Hom.: 7591 AF XY: 0.137 AC XY: 51857 AN XY: 378182

Gnomad4 AFR exome AF: 0.0254

Gnomad4 AMR exome AF: 0.269

Gnomad4 ASJ exome AF: 0.0811

Gnomad4 EAS exome AF: 0.136

Gnomad4 SAS exome AF: 0.144

Gnomad4 FIN exome AF: 0.145

Gnomad4 NFE exome AF: 0.135

Gnomad4 OTH exome AF: 0.127

GnomAD4 genome AF: 0.116 AC: 17669 AN: 152204 Hom.: 1346 Cov.: 32 AF XY: 0.120 AC XY: 8933 AN XY: 74428

Gnomad4 AFR AF: 0.0283

Gnomad4 AMR AF: 0.228

Gnomad4 ASJ AF: 0.0824

Gnomad4 EAS AF: 0.169

Gnomad4 SAS AF: 0.145

Gnomad4 FIN AF: 0.146

Gnomad4 NFE AF: 0.136

Gnomad4 OTH AF: 0.123

Alfa AF: 0.132 Hom.: 1963

Bravo AF: 0.117

Asia WGS AF: 0.165 AC: 576 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Sep 23, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.77
Cadd	Benign	7.0
Dann	Benign	0.68
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

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: rs2482424; hg19: chr9-107665751;