rs2253174

Variant names:

• chr9-104858051-G-A
• rs2253174
• NM_005502.4:c.720+471C>T

Your query was ambiguous. Multiple possible variants found:

• chr9-104858051-G-A
• chr9-104858051-G-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.720+471C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.412 in 152,054 control chromosomes in the GnomAD database, including 15,629 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 0.41 (15629 hom., cov: 32)
• Consequence: ABCA1 NM_005502.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.401
• Publications: 7 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=-0.87).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.702 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ABCA1	NM_005502.4	c.720+471C>T		intron_variant	Intron 7 of 49	ENST00000374736.8	NP_005493.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ABCA1	ENST00000374736.8	c.720+471C>T		intron_variant	Intron 7 of 49	1	NM_005502.4	ENSP00000363868.3
ABCA1	ENST00000678995.1	c.720+471C>T		intron_variant	Intron 7 of 49			ENSP00000504612.1
ABCA1	ENST00000423487.6	c.720+471C>T		intron_variant	Intron 7 of 7	2		ENSP00000416623.2

Frequencies

GnomAD3 genomes AF: 0.411 AC: 62496 AN: 151936 Hom.: 15586 Cov.: 32

Gnomad AFR AF: 0.708

Gnomad AMI AF: 0.450

Gnomad AMR AF: 0.364

Gnomad ASJ AF: 0.302

Gnomad EAS AF: 0.428

Gnomad SAS AF: 0.375

Gnomad FIN AF: 0.222

Gnomad MID AF: 0.440

Gnomad NFE AF: 0.277

Gnomad OTH AF: 0.409

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

GnomAD4 genome AF: 0.412 AC: 62600 AN: 152054 Hom.: 15629 Cov.: 32 AF XY: 0.409 AC XY: 30388 AN XY: 74320

African (AFR) AF: 0.709 AC: 29396 AN: 41476

American (AMR) AF: 0.364 AC: 5567 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.302 AC: 1048 AN: 3468

East Asian (EAS) AF: 0.427 AC: 2204 AN: 5162

South Asian (SAS) AF: 0.375 AC: 1808 AN: 4822

European-Finnish (FIN) AF: 0.222 AC: 2340 AN: 10542

Middle Eastern (MID) AF: 0.446 AC: 131 AN: 294

European-Non Finnish (NFE) AF: 0.277 AC: 18822 AN: 67984

Other (OTH) AF: 0.414 AC: 875 AN: 2114

Alfa AF: 0.322 Hom.: 15199

Bravo AF: 0.436

Asia WGS AF: 0.426 AC: 1482 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	1.2
DANN	Benign	0.60
PhyloP100		-0.40
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: rs2253174; hg19: chr9-107620332;