9-104837887-A-G

Variant names:

• chr9-104837887-A-G
• rs2515602
• NM_005502.4:c.1055-320T>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.1055-320T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.474 in 152,100 control chromosomes in the GnomAD database, including 19,686 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 0.47 (19686 hom., cov: 32)
• Consequence: ABCA1 NM_005502.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.434
• Publications: 9 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=-0.91).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.774 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ABCA1	NM_005502.4	c.1055-320T>C		intron_variant	Intron 9 of 49	ENST00000374736.8	NP_005493.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ABCA1	ENST00000374736.8	c.1055-320T>C		intron_variant	Intron 9 of 49	1	NM_005502.4	ENSP00000363868.3
ABCA1	ENST00000678995.1	c.1055-320T>C		intron_variant	Intron 9 of 49			ENSP00000504612.1

Frequencies

GnomAD3 genomes AF: 0.474 AC: 71992 AN: 151982 Hom.: 19638 Cov.: 32

Gnomad AFR AF: 0.732

Gnomad AMI AF: 0.475

Gnomad AMR AF: 0.441

Gnomad ASJ AF: 0.381

Gnomad EAS AF: 0.796

Gnomad SAS AF: 0.452

Gnomad FIN AF: 0.271

Gnomad MID AF: 0.484

Gnomad NFE AF: 0.337

Gnomad OTH AF: 0.468

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

GnomAD4 genome AF: 0.474 AC: 72101 AN: 152100 Hom.: 19686 Cov.: 32 AF XY: 0.472 AC XY: 35095 AN XY: 74358

African (AFR) AF: 0.732 AC: 30379 AN: 41480

American (AMR) AF: 0.442 AC: 6754 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.381 AC: 1323 AN: 3470

East Asian (EAS) AF: 0.795 AC: 4096 AN: 5154

South Asian (SAS) AF: 0.451 AC: 2177 AN: 4826

European-Finnish (FIN) AF: 0.271 AC: 2873 AN: 10588

Middle Eastern (MID) AF: 0.476 AC: 139 AN: 292

European-Non Finnish (NFE) AF: 0.337 AC: 22926 AN: 67972

Other (OTH) AF: 0.474 AC: 1001 AN: 2114

Alfa AF: 0.383 Hom.: 9277

Bravo AF: 0.501

Asia WGS AF: 0.624 AC: 2168 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.45
DANN	Benign	0.20
PhyloP100		-0.43
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: rs2515602; hg19: chr9-107600168;