chr9-104855152-C-T

Variant names:

• chr9-104855152-C-T
• rs2487039
• NM_005502.4:c.720+3370G>A

Variant summary

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

The NM_005502.4(ABCA1):​c.720+3370G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.137 in 982,936 control chromosomes in the GnomAD database, including 9,855 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 0.14 (1811 hom., cov: 32)
  • Exomes 𝑓: 0.14 (8044 hom.)
• Consequence: ABCA1 NM_005502.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0410
• Publications: 11 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: Orphanet, Labcorp Genetics (formerly Invitae), G2P
• 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=-0.91).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.317 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ABCA1	NM_005502.4	MANE Select	c.720+3370G>A		intron	N/A	NP_005493.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ABCA1	ENST00000374736.8	TSL:1 MANE Select	c.720+3370G>A		intron	N/A	ENSP00000363868.3	O95477
	ABCA1	ENST00000678995.1		c.720+3370G>A		intron	N/A	ENSP00000504612.1	A0A7I2V5U0

Frequencies

GnomAD3 genomes AF: 0.142 AC: 21593 AN: 152060 Hom.: 1808 Cov.: 32

Gnomad AFR AF: 0.0834

Gnomad AMI AF: 0.268

Gnomad AMR AF: 0.218

Gnomad ASJ AF: 0.182

Gnomad EAS AF: 0.331

Gnomad SAS AF: 0.249

Gnomad FIN AF: 0.109

Gnomad MID AF: 0.174

Gnomad NFE AF: 0.139

Gnomad OTH AF: 0.167

GnomAD4 exome AF: 0.136 AC: 113145 AN: 830756 Hom.: 8044 Cov.: 26 AF XY: 0.137 AC XY: 52615 AN XY: 383642

African (AFR) AF: 0.0734 AC: 1155 AN: 15744

American (AMR) AF: 0.248 AC: 243 AN: 978

Ashkenazi Jewish (ASJ) AF: 0.189 AC: 968 AN: 5116

East Asian (EAS) AF: 0.332 AC: 1196 AN: 3602

South Asian (SAS) AF: 0.238 AC: 3897 AN: 16390

European-Finnish (FIN) AF: 0.0833 AC: 23 AN: 276

Middle Eastern (MID) AF: 0.223 AC: 359 AN: 1610

European-Non Finnish (NFE) AF: 0.133 AC: 100913 AN: 759810

Other (OTH) AF: 0.161 AC: 4391 AN: 27230

GnomAD4 genome AF: 0.142 AC: 21629 AN: 152180 Hom.: 1811 Cov.: 32 AF XY: 0.146 AC XY: 10825 AN XY: 74394

African (AFR) AF: 0.0837 AC: 3479 AN: 41556

American (AMR) AF: 0.219 AC: 3341 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.182 AC: 631 AN: 3472

East Asian (EAS) AF: 0.330 AC: 1700 AN: 5148

South Asian (SAS) AF: 0.250 AC: 1205 AN: 4822

European-Finnish (FIN) AF: 0.109 AC: 1154 AN: 10590

Middle Eastern (MID) AF: 0.170 AC: 50 AN: 294

European-Non Finnish (NFE) AF: 0.139 AC: 9462 AN: 67992

Other (OTH) AF: 0.172 AC: 363 AN: 2112

Alfa AF: 0.148 Hom.: 2998

Bravo AF: 0.148

Asia WGS AF: 0.260 AC: 901 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	3.0
DANN	Benign	0.60
PhyloP100		-0.041
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
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: rs2487039; hg19: chr9-107617433;