rs4149271

Variant summary

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

The NM_005502.4(ABCA1):​c.421+1033C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.244 in 118,522 control chromosomes in the GnomAD database, including 3,172 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 0.24 ( 3172 hom., cov: 22)

Consequence

ABCA1
NM_005502.4 intron

Scores

2

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.18
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=-0.84).
BA1
GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.411 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
ABCA1NM_005502.4 linkc.421+1033C>T intron_variant Intron 5 of 49 ENST00000374736.8 NP_005493.2 O95477B7XCW9B2RUU2

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
ABCA1ENST00000374736.8 linkc.421+1033C>T intron_variant Intron 5 of 49 1 NM_005502.4 ENSP00000363868.3 O95477
ABCA1ENST00000678995.1 linkc.421+1033C>T intron_variant Intron 5 of 49 ENSP00000504612.1 A0A7I2V5U0
ABCA1ENST00000423487.6 linkc.421+1033C>T intron_variant Intron 5 of 7 2 ENSP00000416623.2 B1AMI2
ABCA1ENST00000374733.1 linkc.241+1033C>T intron_variant Intron 4 of 4 2 ENSP00000363865.1 B1AMI1

Frequencies

GnomAD3 genomes
AF:
0.244
AC:
28890
AN:
118458
Hom.:
3178
Cov.:
22
show subpopulations
Gnomad AFR
AF:
0.203
Gnomad AMI
AF:
0.335
Gnomad AMR
AF:
0.289
Gnomad ASJ
AF:
0.255
Gnomad EAS
AF:
0.324
Gnomad SAS
AF:
0.429
Gnomad FIN
AF:
0.258
Gnomad MID
AF:
0.322
Gnomad NFE
AF:
0.239
Gnomad OTH
AF:
0.249
We have no GnomAD4 exomes data on this position. Probably position not covered by the project.
GnomAD4 genome
AF:
0.244
AC:
28902
AN:
118522
Hom.:
3172
Cov.:
22
AF XY:
0.253
AC XY:
14043
AN XY:
55422
show subpopulations
Gnomad4 AFR
AF:
0.203
Gnomad4 AMR
AF:
0.289
Gnomad4 ASJ
AF:
0.255
Gnomad4 EAS
AF:
0.323
Gnomad4 SAS
AF:
0.428
Gnomad4 FIN
AF:
0.258
Gnomad4 NFE
AF:
0.239
Gnomad4 OTH
AF:
0.253
Alfa
AF:
0.208
Hom.:
4484
Bravo
AF:
0.201
Asia WGS
AF:
0.314
AC:
1088
AN:
3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.84
CADD
Benign
10
DANN
Benign
0.67

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.010
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: rs4149271; hg19: chr9-107644287; COSMIC: COSV66058011; API