rs796051873

chr9-104831739-CAGAACTTCCTCTCA-CGTACAGTGGCGTGACCTCAGCTCACTGCAACCTCTGCCTCCTGAGTTCAAGTGATTCTCGTGCCTCAGCCTCCCAAGTAGCTGGGATTchr9-104831739-CAGAACTTCCTCTCA-CGTACAGTGGCGTGACCTCAGCTCACTGCAACCTCTGCCTCCTGAGTTCAAGTGATTCTCGTGCCTCAGCCTCCCAAGTAGCTGGGATTACAGCTCCTGCCACCACGCCCG

Variant summary

Our verdict is Likely pathogenic. Variant got 8 ACMG points: 8P and 0B. PVS1

The NM_005502.4(ABCA1):c.1584_1597delinsAATCCCAGCTACTTGGGAGGCTGAGGCACGAGAATCACTTGAACTCAGGAGGCAGAGGTTGCAGTGAGCTGAGGTCACGCCACTGTAC(p.Asp528GlufsTer23) variant causes a stop gained, frameshift change involving the alteration of a conserved nucleotide. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Variant results in nonsense mediated mRNA decay.

• Frequency: Genomes: not found (cov: 32)
• Consequence: ABCA1 NM_005502.4 stop_gained, frameshift
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 8.95

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 Likely_pathogenic. Variant got 8 ACMG points.

• PVS1: Loss of function variant, product undergoes nonsense mediated mRNA decay. LoF is a known mechanism of disease.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ABCA1	NM_005502.4	c.1584_1597delinsAATCCCAGCTACTTGGGAGGCTGAGGCACGAGAATCACTTGAACTCAGGAGGCAGAGGTTGCAGTGAGCTGAGGTCACGCCACTGTAC	p.Asp528GlufsTer23	stop_gained, frameshift_variant	13/50	ENST00000374736.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ABCA1	ENST00000374736.8	c.1584_1597delinsAATCCCAGCTACTTGGGAGGCTGAGGCACGAGAATCACTTGAACTCAGGAGGCAGAGGTTGCAGTGAGCTGAGGTCACGCCACTGTAC	p.Asp528GlufsTer23	stop_gained, frameshift_variant	13/50	1	NM_005502.4	P1
ABCA1	ENST00000678995.1	c.1584_1597delinsAATCCCAGCTACTTGGGAGGCTGAGGCACGAGAATCACTTGAACTCAGGAGGCAGAGGTTGCAGTGAGCTGAGGTCACGCCACTGTAC	p.Asp528GlufsTer23	stop_gained, frameshift_variant	13/50

Frequencies

GnomAD3 genomes Cov.: 32

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

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs796051873; hg19: chr9-107594021;