9-104832234-A-G

Variant names:

• chr9-104832234-A-G
• rs4149303
• NM_005502.4:c.1509+340T>C

Variant summary

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

The NM_005502.4(ABCA1):​c.1509+340T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.197 in 152,148 control chromosomes in the GnomAD database, including 4,031 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 0.20 (4031 hom., cov: 32)
• Consequence: ABCA1 NM_005502.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.50
• 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=-0.93).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.681 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.1509+340T>C		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.1509+340T>C		intron	N/A	ENSP00000363868.3
	ABCA1	ENST00000678995.1		c.1509+340T>C		intron	N/A	ENSP00000504612.1

Frequencies

GnomAD3 genomes AF: 0.197 AC: 29901 AN: 152032 Hom.: 4029 Cov.: 32

Gnomad AFR AF: 0.290

Gnomad AMI AF: 0.0921

Gnomad AMR AF: 0.189

Gnomad ASJ AF: 0.164

Gnomad EAS AF: 0.700

Gnomad SAS AF: 0.160

Gnomad FIN AF: 0.110

Gnomad MID AF: 0.177

Gnomad NFE AF: 0.123

Gnomad OTH AF: 0.193

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

GnomAD4 genome AF: 0.197 AC: 29938 AN: 152148 Hom.: 4031 Cov.: 32 AF XY: 0.199 AC XY: 14788 AN XY: 74396

African (AFR) AF: 0.290 AC: 12023 AN: 41480

American (AMR) AF: 0.189 AC: 2897 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.164 AC: 570 AN: 3472

East Asian (EAS) AF: 0.700 AC: 3613 AN: 5164

South Asian (SAS) AF: 0.160 AC: 769 AN: 4810

European-Finnish (FIN) AF: 0.110 AC: 1167 AN: 10600

Middle Eastern (MID) AF: 0.167 AC: 49 AN: 294

European-Non Finnish (NFE) AF: 0.123 AC: 8349 AN: 68020

Other (OTH) AF: 0.198 AC: 417 AN: 2108

Alfa AF: 0.146 Hom.: 3036

Bravo AF: 0.213

Asia WGS AF: 0.390 AC: 1354 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.0070
DANN	Benign	0.39
PhyloP100		-1.5
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: rs4149303; hg19: chr9-107594515;