NM_005502.4:c.814-1397C>A

Variant names:

• chr9-104841916-G-T
• rs2472449
• NM_005502.4:c.814-1397C>A

Variant summary

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

The NM_005502.4(ABCA1):​c.814-1397C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.482 in 152,138 control chromosomes in the GnomAD database, including 20,685 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 0.48 (20685 hom., cov: 33)
• Consequence: ABCA1 NM_005502.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0470
• Publications: 7 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=-0.88).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.775 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ABCA1	NM_005502.4	c.814-1397C>A		intron_variant	Intron 8 of 49	ENST00000374736.8	NP_005493.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ABCA1	ENST00000374736.8	c.814-1397C>A		intron_variant	Intron 8 of 49	1	NM_005502.4	ENSP00000363868.3
ABCA1	ENST00000678995.1	c.814-1397C>A		intron_variant	Intron 8 of 49			ENSP00000504612.1

Frequencies

GnomAD3 genomes AF: 0.481 AC: 73180 AN: 152020 Hom.: 20631 Cov.: 33

Gnomad AFR AF: 0.765

Gnomad AMI AF: 0.477

Gnomad AMR AF: 0.440

Gnomad ASJ AF: 0.380

Gnomad EAS AF: 0.796

Gnomad SAS AF: 0.446

Gnomad FIN AF: 0.270

Gnomad MID AF: 0.497

Gnomad NFE AF: 0.335

Gnomad OTH AF: 0.472

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

GnomAD4 genome AF: 0.482 AC: 73295 AN: 152138 Hom.: 20685 Cov.: 33 AF XY: 0.479 AC XY: 35635 AN XY: 74352

African (AFR) AF: 0.766 AC: 31781 AN: 41502

American (AMR) AF: 0.440 AC: 6730 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.380 AC: 1318 AN: 3472

East Asian (EAS) AF: 0.795 AC: 4124 AN: 5186

South Asian (SAS) AF: 0.445 AC: 2149 AN: 4824

European-Finnish (FIN) AF: 0.270 AC: 2857 AN: 10564

Middle Eastern (MID) AF: 0.493 AC: 145 AN: 294

European-Non Finnish (NFE) AF: 0.335 AC: 22749 AN: 67990

Other (OTH) AF: 0.477 AC: 1008 AN: 2112

Alfa AF: 0.391 Hom.: 48376

Bravo AF: 0.510

Asia WGS AF: 0.622 AC: 2160 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	3.8
DANN	Benign	0.68
PhyloP100		0.047
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: rs2472449; hg19: chr9-107604197;