rs3905001

Variant names:

• chr9-104905783-G-C
• rs3905001
• NM_005502.4:c.-92-2012C>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.-92-2012C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.332 in 152,036 control chromosomes in the GnomAD database, including 8,897 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 0.33 (8897 hom., cov: 32)
• Consequence: ABCA1 NM_005502.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0400
• Publications: 10 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=-0.8).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.565 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_005502.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ABCA1	NM_005502.4	MANE Select	c.-92-2012C>G		intron	N/A	NP_005493.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ABCA1	ENST00000374736.8	TSL:1 MANE Select	c.-92-2012C>G		intron	N/A	ENSP00000363868.3
	ABCA1	ENST00000678995.1		c.-92-2012C>G		intron	N/A	ENSP00000504612.1
	ABCA1	ENST00000423487.6	TSL:2	c.-92-2012C>G		intron	N/A	ENSP00000416623.2

Frequencies

GnomAD3 genomes AF: 0.332 AC: 50402 AN: 151918 Hom.: 8895 Cov.: 32

Gnomad AFR AF: 0.413

Gnomad AMI AF: 0.485

Gnomad AMR AF: 0.229

Gnomad ASJ AF: 0.385

Gnomad EAS AF: 0.583

Gnomad SAS AF: 0.303

Gnomad FIN AF: 0.304

Gnomad MID AF: 0.323

Gnomad NFE AF: 0.289

Gnomad OTH AF: 0.307

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

GnomAD4 genome AF: 0.332 AC: 50440 AN: 152036 Hom.: 8897 Cov.: 32 AF XY: 0.331 AC XY: 24606 AN XY: 74316

African (AFR) AF: 0.413 AC: 17117 AN: 41440

American (AMR) AF: 0.229 AC: 3497 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.385 AC: 1335 AN: 3470

East Asian (EAS) AF: 0.582 AC: 3010 AN: 5170

South Asian (SAS) AF: 0.303 AC: 1459 AN: 4818

European-Finnish (FIN) AF: 0.304 AC: 3214 AN: 10570

Middle Eastern (MID) AF: 0.320 AC: 94 AN: 294

European-Non Finnish (NFE) AF: 0.289 AC: 19626 AN: 67970

Other (OTH) AF: 0.306 AC: 646 AN: 2110

Alfa AF: 0.299 Hom.: 972

Bravo AF: 0.331

Asia WGS AF: 0.408 AC: 1418 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	2.8
DANN	Benign	0.55
PhyloP100		0.040
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: rs3905001; hg19: chr9-107668064;