9-104906544-G-C

Variant names:

• chr9-104906544-G-C
• rs2575879
• NM_005502.4:c.-92-2773C>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_005502.4(ABCA1):​c.-92-2773C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.625 in 151,688 control chromosomes in the GnomAD database, including 30,605 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 0.63 (30605 hom., cov: 29)
• Consequence: ABCA1 NM_005502.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.00200
• Publications: 8 publications found

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 Gene-Disease associations (from GenCC):

• hypoalphalipoproteinemia, primary, 1

  Inheritance: AD Classification: DEFINITIVE, LIMITED Submitted by: Ambry Genetics, Labcorp Genetics (formerly Invitae)
• Tangier disease

  Inheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Labcorp Genetics (formerly Invitae), G2P, Orphanet
• apolipoprotein A-I deficiency

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.803 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ABCA1	NM_005502.4	c.-92-2773C>G		intron_variant	Intron 1 of 49	ENST00000374736.8	NP_005493.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ABCA1	ENST00000374736.8	c.-92-2773C>G		intron_variant	Intron 1 of 49	1	NM_005502.4	ENSP00000363868.3
ABCA1	ENST00000678995.1	c.-92-2773C>G		intron_variant	Intron 1 of 49			ENSP00000504612.1
ABCA1	ENST00000423487.6	c.-92-2773C>G		intron_variant	Intron 1 of 7	2		ENSP00000416623.2
ABCA1	ENST00000374733.1	c.-114-17349C>G		intron_variant	Intron 1 of 4	2		ENSP00000363865.1

Frequencies

GnomAD3 genomes AF: 0.625 AC: 94755 AN: 151570 Hom.: 30562 Cov.: 29

Gnomad AFR AF: 0.761

Gnomad AMI AF: 0.827

Gnomad AMR AF: 0.524

Gnomad ASJ AF: 0.622

Gnomad EAS AF: 0.824

Gnomad SAS AF: 0.645

Gnomad FIN AF: 0.488

Gnomad MID AF: 0.639

Gnomad NFE AF: 0.568

Gnomad OTH AF: 0.610

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.625 AC: 94856 AN: 151688 Hom.: 30605 Cov.: 29 AF XY: 0.620 AC XY: 45960 AN XY: 74084

African (AFR) AF: 0.761 AC: 31503 AN: 41390

American (AMR) AF: 0.523 AC: 7971 AN: 15234

Ashkenazi Jewish (ASJ) AF: 0.622 AC: 2159 AN: 3470

East Asian (EAS) AF: 0.824 AC: 4215 AN: 5116

South Asian (SAS) AF: 0.644 AC: 3088 AN: 4794

European-Finnish (FIN) AF: 0.488 AC: 5123 AN: 10508

Middle Eastern (MID) AF: 0.636 AC: 187 AN: 294

European-Non Finnish (NFE) AF: 0.568 AC: 38565 AN: 67866

Other (OTH) AF: 0.614 AC: 1297 AN: 2112

Alfa AF: 0.589 Hom.: 3366

Bravo AF: 0.634

Asia WGS AF: 0.742 AC: 2578 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	2.3
DANN	Benign	0.65
PhyloP100		-0.0020
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs2575879; hg19: chr9-107668825;