rs10512337

Variant names:

• chr9-104918449-G-A
• rs10512337
• NM_005502.4:c.-93+9486C>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.-93+9486C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.112 in 152,134 control chromosomes in the GnomAD database, including 1,178 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 0.11 (1178 hom., cov: 32)
• Consequence: ABCA1 NM_005502.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.63
• Publications: 6 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

LOC124902239 (HGNC:):

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.194 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ABCA1	NM_005502.4	c.-93+9486C>T		intron_variant	Intron 1 of 49	ENST00000374736.8	NP_005493.2
LOC124902239	XR_007061706.1	n.749G>A		non_coding_transcript_exon_variant	Exon 1 of 3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ABCA1	ENST00000374736.8	c.-93+9486C>T		intron_variant	Intron 1 of 49	1	NM_005502.4	ENSP00000363868.3

Frequencies

GnomAD3 genomes AF: 0.112 AC: 17045 AN: 152016 Hom.: 1177 Cov.: 32

Gnomad AFR AF: 0.198

Gnomad AMI AF: 0.0921

Gnomad AMR AF: 0.101

Gnomad ASJ AF: 0.0329

Gnomad EAS AF: 0.00173

Gnomad SAS AF: 0.0573

Gnomad FIN AF: 0.0818

Gnomad MID AF: 0.0348

Gnomad NFE AF: 0.0851

Gnomad OTH AF: 0.0852

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

GnomAD4 genome AF: 0.112 AC: 17067 AN: 152134 Hom.: 1178 Cov.: 32 AF XY: 0.110 AC XY: 8166 AN XY: 74390

African (AFR) AF: 0.198 AC: 8207 AN: 41482

American (AMR) AF: 0.101 AC: 1540 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.0329 AC: 114 AN: 3468

East Asian (EAS) AF: 0.00174 AC: 9 AN: 5178

South Asian (SAS) AF: 0.0565 AC: 273 AN: 4834

European-Finnish (FIN) AF: 0.0818 AC: 865 AN: 10580

Middle Eastern (MID) AF: 0.0374 AC: 11 AN: 294

European-Non Finnish (NFE) AF: 0.0851 AC: 5787 AN: 68002

Other (OTH) AF: 0.0839 AC: 177 AN: 2110

Alfa AF: 0.0888 Hom.: 1224

Bravo AF: 0.117

Asia WGS AF: 0.0360 AC: 125 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	6.5
DANN	Benign	0.72
PhyloP100		-1.6
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: rs10512337; hg19: chr9-107680730;