rs2020927

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_005502.4(ABCA1):​c.5927+18T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.158 in 1,519,884 control chromosomes in the GnomAD database, including 26,755 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.24 ( 6611 hom., cov: 32)
Exomes 𝑓: 0.15 ( 20144 hom. )

Consequence

ABCA1
NM_005502.4 intron

Scores

2

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:5

Conservation

PhyloP100: 0.276
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 -20 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.87).
BP6
Variant 9-104790904-A-G is Benign according to our data. Variant chr9-104790904-A-G is described in ClinVar as [Benign]. Clinvar id is 928662.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr9-104790904-A-G is described in Lovd as [Benign].
BA1
GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.495 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
ABCA1NM_005502.4 linkuse as main transcriptc.5927+18T>C intron_variant ENST00000374736.8 NP_005493.2 O95477B7XCW9B2RUU2
NIPSNAP3BXR_007061325.1 linkuse as main transcriptn.*5A>G downstream_gene_variant

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
ABCA1ENST00000374736.8 linkuse as main transcriptc.5927+18T>C intron_variant 1 NM_005502.4 ENSP00000363868.3 O95477
ABCA1ENST00000678995.1 linkuse as main transcriptc.5933+18T>C intron_variant ENSP00000504612.1 A0A7I2V5U0

Frequencies

GnomAD3 genomes
AF:
0.241
AC:
36635
AN:
152004
Hom.:
6600
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.501
Gnomad AMI
AF:
0.211
Gnomad AMR
AF:
0.163
Gnomad ASJ
AF:
0.120
Gnomad EAS
AF:
0.419
Gnomad SAS
AF:
0.227
Gnomad FIN
AF:
0.0620
Gnomad MID
AF:
0.313
Gnomad NFE
AF:
0.123
Gnomad OTH
AF:
0.223
GnomAD3 exomes
AF:
0.182
AC:
45660
AN:
250776
Hom.:
6149
AF XY:
0.177
AC XY:
24038
AN XY:
135556
show subpopulations
Gnomad AFR exome
AF:
0.513
Gnomad AMR exome
AF:
0.148
Gnomad ASJ exome
AF:
0.113
Gnomad EAS exome
AF:
0.428
Gnomad SAS exome
AF:
0.218
Gnomad FIN exome
AF:
0.0652
Gnomad NFE exome
AF:
0.125
Gnomad OTH exome
AF:
0.159
GnomAD4 exome
AF:
0.149
AC:
203445
AN:
1367762
Hom.:
20144
Cov.:
20
AF XY:
0.149
AC XY:
102375
AN XY:
686210
show subpopulations
Gnomad4 AFR exome
AF:
0.520
Gnomad4 AMR exome
AF:
0.149
Gnomad4 ASJ exome
AF:
0.115
Gnomad4 EAS exome
AF:
0.413
Gnomad4 SAS exome
AF:
0.215
Gnomad4 FIN exome
AF:
0.0677
Gnomad4 NFE exome
AF:
0.125
Gnomad4 OTH exome
AF:
0.177
GnomAD4 genome
AF:
0.241
AC:
36690
AN:
152122
Hom.:
6611
Cov.:
32
AF XY:
0.236
AC XY:
17516
AN XY:
74372
show subpopulations
Gnomad4 AFR
AF:
0.501
Gnomad4 AMR
AF:
0.163
Gnomad4 ASJ
AF:
0.120
Gnomad4 EAS
AF:
0.419
Gnomad4 SAS
AF:
0.226
Gnomad4 FIN
AF:
0.0620
Gnomad4 NFE
AF:
0.123
Gnomad4 OTH
AF:
0.223
Alfa
AF:
0.145
Hom.:
2636
Bravo
AF:
0.260
Asia WGS
AF:
0.366
AC:
1265
AN:
3472

ClinVar

Significance: Benign
Submissions summary: Benign:5
Revision: criteria provided, multiple submitters, no conflicts
LINK: link

Submissions by phenotype

not provided Benign:3
Benign, criteria provided, single submitterclinical testingGeneDxOct 01, 2018- -
Benign, criteria provided, single submitterclinical testingLabcorp Genetics (formerly Invitae), LabcorpJan 31, 2024- -
Benign, criteria provided, single submitternot providedBreakthrough Genomics, Breakthrough Genomics-- -
not specified Benign:1
Benign, criteria provided, single submitterclinical testingWomen's Health and Genetics/Laboratory Corporation of America, LabCorpAug 12, 2019- -
Tangier disease Benign:1
Benign, criteria provided, single submitterclinical testingGenome-Nilou LabJul 14, 2021- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.87
CADD
Benign
6.4
DANN
Benign
0.61

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: rs2020927; hg19: chr9-107553185; COSMIC: COSV66067802; API