9-104903697-C-G

Position:

chr9-104903697-C-G

Variant summary

Our verdict is Benign. Variant got -18 ACMG points: 0P and 18B. BP4_ModerateBP6_Very_StrongBA1

The ENST00000374736.8(ABCA1):c.-18G>C variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.13 in 1,571,042 control chromosomes in the GnomAD database, including 14,702 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.11 ( 1173 hom., cov: 32)

Exomes 𝑓: 0.13 ( 13529 hom. )

Consequence

ABCA1
ENST00000374736.8 5_prime_UTR

Scores

Clinical Significance

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

Conservation

PhyloP100: 0.332

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -18 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.44).

BP6

Variant 9-104903697-C-G is Benign according to our data. Variant chr9-104903697-C-G is described in ClinVar as [Benign]. Clinvar id is 364468.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr9-104903697-C-G is described in Lovd as [Benign].

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.-18G>C		5_prime_UTR_variant	2/50	ENST00000374736.8	NP_005493.2

Ensembl

Gene	Transcript	HGVSc	Effect	#exon/exons	TSL	MANE	Protein	Appris
ABCA1	ENST00000374736.8 linkuse as main transcript	c.-18G>C	5_prime_UTR_variant	2/50	1	NM_005502.4	ENSP00000363868	P1
ABCA1	ENST00000423487.6 linkuse as main transcript	c.-18G>C	5_prime_UTR_variant	2/8	2		ENSP00000416623
ABCA1	ENST00000678995.1 linkuse as main transcript	c.-18G>C	5_prime_UTR_variant	2/50			ENSP00000504612
ABCA1	ENST00000374733.1 linkuse as main transcript	c.-114-14502G>C	intron_variant		2		ENSP00000363865

Frequencies

GnomAD3 genomes

AF:

0.107

AC:

16213

AN:

152158

Hom.:

1171

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:

0.182

Gnomad SAS

AF:

0.243

Gnomad FIN

AF:

0.112

Gnomad MID

AF:

0.0981

Gnomad NFE

AF:

0.127

Gnomad OTH

AF:

0.112

GnomAD3 exomes

AF:

0.145

AC:

26746

AN:

184886

Hom.:

2289

AF XY:

0.148

AC XY:

14545

AN XY:

98186

show subpopulations

Gnomad AFR exome

AF:

0.0231

Gnomad AMR exome

AF:

0.199

Gnomad ASJ exome

AF:

0.148

Gnomad EAS exome

AF:

0.168

Gnomad SAS exome

AF:

0.228

Gnomad FIN exome

AF:

0.105

Gnomad NFE exome

AF:

0.121

Gnomad OTH exome

AF:

0.145

GnomAD4 exome

AF:

0.132

AC:

187609

AN:

1418766

Hom.:

13529

Cov.:

AF XY:

0.135

AC XY:

94748

AN XY:

701630

show subpopulations

Gnomad4 AFR exome

AF:

0.0194

Gnomad4 AMR exome

AF:

0.190

Gnomad4 ASJ exome

AF:

0.150

Gnomad4 EAS exome

AF:

0.195

Gnomad4 SAS exome

AF:

0.225

Gnomad4 FIN exome

AF:

0.105

Gnomad4 NFE exome

AF:

0.125

Gnomad4 OTH exome

AF:

0.142

GnomAD4 genome

AF:

0.107

AC:

16227

AN:

152276

Hom.:

1173

Cov.:

AF XY:

0.110

AC XY:

8163

AN XY:

74462

show subpopulations

Gnomad4 AFR

AF:

0.0251

Gnomad4 AMR

AF:

0.158

Gnomad4 ASJ

AF:

0.144

Gnomad4 EAS

AF:

0.182

Gnomad4 SAS

AF:

0.242

Gnomad4 FIN

AF:

0.112

Gnomad4 NFE

AF:

0.127

Gnomad4 OTH

AF:

0.119

Alfa

AF:

0.0757

Hom.:

116

Bravo

AF:

0.106

Asia WGS

AF:

0.217

AC:

751

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	Apr 01, 2019	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

Women's Health and Genetics/Laboratory Corporation of America, LabCorp

Sep 20, 2019

- -

Tangier disease

Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jan 13, 2018

This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -

Hypoalphalipoproteinemia, primary, 1

Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jan 13, 2018

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.44

CADD

Benign

DANN

Benign

0.85

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.0

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