chr9-104856400-T-C

Variant names:

• chr9-104856400-T-C
• rs2472384
• NM_005502.4:c.720+2122A>G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_005502.4(ABCA1):​c.720+2122A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.385 in 151,960 control chromosomes in the GnomAD database, including 13,084 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 0.38 (13084 hom., cov: 32)
• Consequence: ABCA1 NM_005502.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.118

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.619 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ABCA1	NM_005502.4	c.720+2122A>G		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+2122A>G		intron_variant	Intron 7 of 49	1	NM_005502.4	ENSP00000363868.3
ABCA1	ENST00000678995.1	c.720+2122A>G		intron_variant	Intron 7 of 49			ENSP00000504612.1
ABCA1	ENST00000423487.6	c.721-312A>G		intron_variant	Intron 7 of 7	2		ENSP00000416623.2

Frequencies

GnomAD3 genomes AF: 0.384 AC: 58368 AN: 151844 Hom.: 13045 Cov.: 32

Gnomad AFR AF: 0.625

Gnomad AMI AF: 0.448

Gnomad AMR AF: 0.347

Gnomad ASJ AF: 0.278

Gnomad EAS AF: 0.444

Gnomad SAS AF: 0.374

Gnomad FIN AF: 0.221

Gnomad MID AF: 0.396

Gnomad NFE AF: 0.273

Gnomad OTH AF: 0.377

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

GnomAD4 genome AF: 0.385 AC: 58473 AN: 151960 Hom.: 13084 Cov.: 32 AF XY: 0.383 AC XY: 28434 AN XY: 74278

Gnomad4 AFR AF: 0.626

Gnomad4 AMR AF: 0.347

Gnomad4 ASJ AF: 0.278

Gnomad4 EAS AF: 0.443

Gnomad4 SAS AF: 0.373

Gnomad4 FIN AF: 0.221

Gnomad4 NFE AF: 0.273

Gnomad4 OTH AF: 0.381

Alfa AF: 0.297 Hom.: 8870

Bravo AF: 0.405

Asia WGS AF: 0.427 AC: 1485 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	7.3
DANN	Benign	0.43
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs2472384; hg19: chr9-107618681;