rs2777799

Positions:

• chr9-104796778-G-A

Variant summary

Our verdict is Benign. Variant got -11 ACMG points: 0P and 11B. BP4_Moderate BP6 BA1

The NM_005502.4(ABCA1):​c.5122-354C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.865 in 152,130 control chromosomes in the GnomAD database, including 57,143 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in Lovd as Benign (no stars).

• Frequency: Genomes: 𝑓 0.87 (57143 hom., cov: 32)
• Consequence: ABCA1 NM_005502.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.695

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 -11 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.42).
• BP6: Variant 9-104796778-G-A is Benign according to our data. Variant chr9-104796778-G-A is described in Lovd as [Benign].
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.976 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ABCA1	NM_005502.4	c.5122-354C>T		intron_variant		ENST00000374736.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ABCA1	ENST00000374736.8	c.5122-354C>T		intron_variant		1	NM_005502.4	P1
ABCA1	ENST00000678995.1	c.5128-354C>T		intron_variant

Frequencies

GnomAD3 genomes AF: 0.865 AC: 131506 AN: 152012 Hom.: 57092 Cov.: 32

Gnomad AFR AF: 0.785

Gnomad AMI AF: 0.977

Gnomad AMR AF: 0.905

Gnomad ASJ AF: 0.850

Gnomad EAS AF: 0.999

Gnomad SAS AF: 0.867

Gnomad FIN AF: 0.910

Gnomad MID AF: 0.826

Gnomad NFE AF: 0.887

Gnomad OTH AF: 0.861

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

GnomAD4 genome AF: 0.865 AC: 131612 AN: 152130 Hom.: 57143 Cov.: 32 AF XY: 0.867 AC XY: 64508 AN XY: 74372

Gnomad4 AFR AF: 0.785

Gnomad4 AMR AF: 0.905

Gnomad4 ASJ AF: 0.850

Gnomad4 EAS AF: 0.999

Gnomad4 SAS AF: 0.867

Gnomad4 FIN AF: 0.910

Gnomad4 NFE AF: 0.887

Gnomad4 OTH AF: 0.862

Alfa AF: 0.879 Hom.: 49298

Bravo AF: 0.861

Asia WGS AF: 0.943 AC: 3278 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.42
CADD	Benign	12
DANN	Benign	0.82

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: rs2777799; hg19: chr9-107559059;