9-104855152-C-T

Position:

• chr9-104855152-C-T

Variant summary

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

The NM_005502.4(ABCA1):​c.720+3370G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.137 in 982,936 control chromosomes in the GnomAD database, including 9,855 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 0.14 (1811 hom., cov: 32)
  • Exomes 𝑓: 0.14 (8044 hom.)
• Consequence: ABCA1 NM_005502.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0410

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=-0.91).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.317 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ABCA1	NM_005502.4	c.720+3370G>A		intron_variant		ENST00000374736.8	NP_005493.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ABCA1	ENST00000374736.8	c.720+3370G>A		intron_variant		1	NM_005502.4	ENSP00000363868	P1
ABCA1	ENST00000678995.1	c.720+3370G>A		intron_variant				ENSP00000504612

Frequencies

GnomAD3 genomes AF: 0.142 AC: 21593 AN: 152060 Hom.: 1808 Cov.: 32

Gnomad AFR AF: 0.0834

Gnomad AMI AF: 0.268

Gnomad AMR AF: 0.218

Gnomad ASJ AF: 0.182

Gnomad EAS AF: 0.331

Gnomad SAS AF: 0.249

Gnomad FIN AF: 0.109

Gnomad MID AF: 0.174

Gnomad NFE AF: 0.139

Gnomad OTH AF: 0.167

GnomAD4 exome AF: 0.136 AC: 113145 AN: 830756 Hom.: 8044 Cov.: 26 AF XY: 0.137 AC XY: 52615 AN XY: 383642

Gnomad4 AFR exome AF: 0.0734

Gnomad4 AMR exome AF: 0.248

Gnomad4 ASJ exome AF: 0.189

Gnomad4 EAS exome AF: 0.332

Gnomad4 SAS exome AF: 0.238

Gnomad4 FIN exome AF: 0.0833

Gnomad4 NFE exome AF: 0.133

Gnomad4 OTH exome AF: 0.161

GnomAD4 genome AF: 0.142 AC: 21629 AN: 152180 Hom.: 1811 Cov.: 32 AF XY: 0.146 AC XY: 10825 AN XY: 74394

Gnomad4 AFR AF: 0.0837

Gnomad4 AMR AF: 0.219

Gnomad4 ASJ AF: 0.182

Gnomad4 EAS AF: 0.330

Gnomad4 SAS AF: 0.250

Gnomad4 FIN AF: 0.109

Gnomad4 NFE AF: 0.139

Gnomad4 OTH AF: 0.172

Alfa AF: 0.150 Hom.: 2394

Bravo AF: 0.148

Asia WGS AF: 0.260 AC: 901 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	3.0
DANN	Benign	0.60
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: rs2487039; hg19: chr9-107617433;