Variant 9-104903754-GC-GCC details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP6_Very_StrongBA1

The NM_005502.4(ABCA1):c.-76dupG variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.123 in 1,369,130 control chromosomes in the GnomAD database, including 12,187 homozygotes. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.11 ( 1169 hom., cov: 30)

Exomes 𝑓: 0.12 ( 11018 hom. )

Consequence

ABCA1
NM_005502.4 5_prime_UTR

Scores

Not classified

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: 1.30

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]

ABCA1 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -16 ACMG points.

BP6

Variant 9-104903754-G-GC is Benign according to our data. Variant chr9-104903754-G-GC is described in ClinVar as [Benign]. Clinvar id is 364470.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.231 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ABCA1	NM_005502.4 linkuse as main transcript	c.-76dupG		5_prime_UTR_variant	2/50	ENST00000374736.8	NP_005493.2	O95477B7XCW9B2RUU2

Ensembl

Gene	Transcript	HGVSc	Effect	#exon/exons	TSL	MANE	Protein	UniProt
ABCA1	ENST00000374736.8 linkuse as main transcript	c.-76dupG	5_prime_UTR_variant	2/50	1	NM_005502.4	ENSP00000363868.3	O95477
ABCA1	ENST00000678995.1 linkuse as main transcript	c.-76dupG	5_prime_UTR_variant	2/50			ENSP00000504612.1	A0A7I2V5U0
ABCA1	ENST00000423487.6 linkuse as main transcript	c.-76dupG	5_prime_UTR_variant	2/8	2		ENSP00000416623.2	B1AMI2
ABCA1	ENST00000374733.1 linkuse as main transcript	c.-114-14560dupG	intron_variant		2		ENSP00000363865.1	B1AMI1

Frequencies

GnomAD3 genomes

AF:

0.106

AC:

16192

AN:

152098

Hom.:

1167

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0252

Gnomad AMI

AF:

0.0592

Gnomad AMR

AF:

0.158

Gnomad ASJ

AF:

0.144

Gnomad EAS

AF:

0.180

Gnomad SAS

AF:

0.243

Gnomad FIN

AF:

0.111

Gnomad MID

AF:

0.0981

Gnomad NFE

AF:

0.127

Gnomad OTH

AF:

0.113

GnomAD4 exome

AF:

0.125

AC:

152010

AN:

1216914

Hom.:

11018

Cov.:

AF XY:

0.129

AC XY:

78544

AN XY:

609266

show subpopulations

Gnomad4 AFR exome

AF:

0.0194

Gnomad4 AMR exome

AF:

0.191

Gnomad4 ASJ exome

AF:

0.147

Gnomad4 EAS exome

AF:

0.196

Gnomad4 SAS exome

AF:

0.220

Gnomad4 FIN exome

AF:

0.104

Gnomad4 NFE exome

AF:

0.115

Gnomad4 OTH exome

AF:

0.135

GnomAD4 genome

AF:

0.106

AC:

16206

AN:

152216

Hom.:

1169

Cov.:

AF XY:

0.109

AC XY:

8139

AN XY:

74398

show subpopulations

Gnomad4 AFR

AF:

0.0251

Gnomad4 AMR

AF:

0.158

Gnomad4 ASJ

AF:

0.144

Gnomad4 EAS

AF:

0.180

Gnomad4 SAS

AF:

0.243

Gnomad4 FIN

AF:

0.111

Gnomad4 NFE

AF:

0.127

Gnomad4 OTH

AF:

0.120

Alfa

AF:

0.113

Hom.:

144

Bravo

AF:

0.106

Asia WGS

AF:

0.217

AC:

751

AN:

3476

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

Familial High Density Lipoprotein Deficiency

Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jun 14, 2016

- -

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Aug 30, 2018

- -

Tangier disease

Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jun 14, 2016

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over