chr9-104914930-G-C

Variant names:

• chr9-104914930-G-C
• rs4149264
• NM_005502.4:c.-92-11159C>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.-92-11159C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.177 in 152,072 control chromosomes in the GnomAD database, including 2,571 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 0.18 (2571 hom., cov: 32)
• Consequence: ABCA1 NM_005502.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0620
• 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

ENSG00000306712 (HGNC:):

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.199 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ABCA1	NM_005502.4	c.-92-11159C>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.-92-11159C>G		intron_variant	Intron 1 of 49	1	NM_005502.4	ENSP00000363868.3

Frequencies

GnomAD3 genomes AF: 0.178 AC: 26992 AN: 151954 Hom.: 2575 Cov.: 32

Gnomad AFR AF: 0.133

Gnomad AMI AF: 0.150

Gnomad AMR AF: 0.158

Gnomad ASJ AF: 0.287

Gnomad EAS AF: 0.175

Gnomad SAS AF: 0.201

Gnomad FIN AF: 0.168

Gnomad MID AF: 0.389

Gnomad NFE AF: 0.202

Gnomad OTH AF: 0.206

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

GnomAD4 genome AF: 0.177 AC: 26983 AN: 152072 Hom.: 2571 Cov.: 32 AF XY: 0.177 AC XY: 13176 AN XY: 74330

African (AFR) AF: 0.133 AC: 5517 AN: 41480

American (AMR) AF: 0.157 AC: 2403 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.287 AC: 995 AN: 3472

East Asian (EAS) AF: 0.174 AC: 901 AN: 5170

South Asian (SAS) AF: 0.202 AC: 975 AN: 4818

European-Finnish (FIN) AF: 0.168 AC: 1780 AN: 10568

Middle Eastern (MID) AF: 0.384 AC: 113 AN: 294

European-Non Finnish (NFE) AF: 0.202 AC: 13733 AN: 67976

Other (OTH) AF: 0.203 AC: 429 AN: 2110

Alfa AF: 0.186 Hom.: 385

Bravo AF: 0.175

Asia WGS AF: 0.187 AC: 647 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	1.2
DANN	Benign	0.42
PhyloP100		-0.062
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: rs4149264; hg19: chr9-107677211; COSMIC: COSV66058169;