rs4149338

Variant summary

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

The NM_005502.4(ABCA1):c.*693C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.336 in 152,270 control chromosomes in the GnomAD database, including 9,305 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.34 ( 9297 hom., cov: 31)

Exomes 𝑓: 0.22 ( 8 hom. )

Consequence

ABCA1
NM_005502.4 3_prime_UTR

Scores

Clinical Significance

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

Conservation

PhyloP100: 0.712

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:

NIPSNAP3B (HGNC:):

NIPSNAP3B links:

Genome browser will be placed here

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 9-104783622-G-A is Benign according to our data. Variant chr9-104783622-G-A is described in ClinVar as [Benign]. Clinvar id is 364361.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.736 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ABCA1	NM_005502.4 linkuse as main transcript	c.*693C>T		3_prime_UTR_variant	50/50	ENST00000374736.8
NIPSNAP3B	XR_007061325.1 linkuse as main transcript	n.960-3995G>A		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ABCA1	ENST00000374736.8 linkuse as main transcript	c.*693C>T		3_prime_UTR_variant	50/50	1	NM_005502.4	P1
ABCA1	ENST00000678995.1 linkuse as main transcript	c.*693C>T		3_prime_UTR_variant	50/50

Frequencies

GnomAD3 genomes

AF:

0.336

AC:

51078

AN:

151852

Hom.:

9276

Cov.:

show subpopulations

Gnomad AFR

AF:

0.375

Gnomad AMI

AF:

0.279

Gnomad AMR

AF:

0.392

Gnomad ASJ

AF:

0.218

Gnomad EAS

AF:

0.756

Gnomad SAS

AF:

0.344

Gnomad FIN

AF:

0.282

Gnomad MID

AF:

0.294

Gnomad NFE

AF:

0.284

Gnomad OTH

AF:

0.324

GnomAD4 exome

AF:

0.223

AC:

AN:

300

Hom.:

Cov.:

AF XY:

0.250

AC XY:

AN XY:

188

show subpopulations

Gnomad4 AFR exome

AF:

0.500

Gnomad4 AMR exome

AF:

0.231

Gnomad4 SAS exome

AF:

0.500

Gnomad4 FIN exome

AF:

0.333

Gnomad4 NFE exome

AF:

0.214

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.337

AC:

51141

AN:

151970

Hom.:

9297

Cov.:

AF XY:

0.338

AC XY:

25125

AN XY:

74258

show subpopulations

Gnomad4 AFR

AF:

0.376

Gnomad4 AMR

AF:

0.392

Gnomad4 ASJ

AF:

0.218

Gnomad4 EAS

AF:

0.756

Gnomad4 SAS

AF:

0.344

Gnomad4 FIN

AF:

0.282

Gnomad4 NFE

AF:

0.284

Gnomad4 OTH

AF:

0.330

Alfa

AF:

0.301

Hom.:

14968

Bravo

AF:

0.350

Asia WGS

AF:

0.579

AC:

2011

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

May 08, 2021

- -

Hypoalphalipoproteinemia, primary, 1

Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jan 12, 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. -

Tangier disease

Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jan 12, 2018

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.87

Cadd

Benign

2.0

Dann

Benign

0.65

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