rs2740491

Positions:

• chr9-104896104-G-A
• chr9-104896104-G-C

Variant summary

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

The NM_005502.4(ABCA1):​c.67-6909C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.467 in 152,054 control chromosomes in the GnomAD database, including 18,735 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 (18735 hom., cov: 32)
• Consequence: ABCA1 NM_005502.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.274

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=-0.99).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.714 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ABCA1	NM_005502.4	c.67-6909C>T		intron_variant		ENST00000374736.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ABCA1	ENST00000374736.8	c.67-6909C>T		intron_variant		1	NM_005502.4	P1
ABCA1	ENST00000374733.1	c.-114-6909C>T		intron_variant		2
ABCA1	ENST00000423487.6	c.67-6909C>T		intron_variant		2
ABCA1	ENST00000678995.1	c.67-6909C>T		intron_variant

Frequencies

GnomAD3 genomes AF: 0.467 AC: 70952 AN: 151936 Hom.: 18709 Cov.: 32

Gnomad AFR AF: 0.721

Gnomad AMI AF: 0.491

Gnomad AMR AF: 0.366

Gnomad ASJ AF: 0.456

Gnomad EAS AF: 0.315

Gnomad SAS AF: 0.524

Gnomad FIN AF: 0.282

Gnomad MID AF: 0.516

Gnomad NFE AF: 0.372

Gnomad OTH AF: 0.464

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

GnomAD4 genome AF: 0.467 AC: 71033 AN: 152054 Hom.: 18735 Cov.: 32 AF XY: 0.459 AC XY: 34131 AN XY: 74328

Gnomad4 AFR AF: 0.721

Gnomad4 AMR AF: 0.365

Gnomad4 ASJ AF: 0.456

Gnomad4 EAS AF: 0.315

Gnomad4 SAS AF: 0.523

Gnomad4 FIN AF: 0.282

Gnomad4 NFE AF: 0.372

Gnomad4 OTH AF: 0.467

Alfa AF: 0.363 Hom.: 1477

Bravo AF: 0.481

Asia WGS AF: 0.465 AC: 1615 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
CADD	Benign	1.1
DANN	Benign	0.40

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

Publications

LitVar

Other links and lift over

dbSNP: rs2740491; hg19: chr9-107658385; COSMIC: COSV66058092;