rs2487039

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

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

Scores

2

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.0410
Variant links:
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]

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ACMG classification

Classification made for transcript

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
ABCA1NM_005502.4 linkuse as main transcriptc.720+3370G>A intron_variant ENST00000374736.8 NP_005493.2

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
ABCA1ENST00000374736.8 linkuse as main transcriptc.720+3370G>A intron_variant 1 NM_005502.4 ENSP00000363868 P1
ABCA1ENST00000678995.1 linkuse as main transcriptc.720+3370G>A intron_variant ENSP00000504612

Frequencies

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

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs2487039; hg19: chr9-107617433; API