rs7035693

Positions:

• chr9-104921184-A-G

Variant summary

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

The NM_005502.4(ABCA1):​c.-93+6751T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.144 in 152,174 control chromosomes in the GnomAD database, including 2,387 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 0.14 (2387 hom., cov: 33)
• Consequence: ABCA1 NM_005502.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.369

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]

LOC124902239 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.307 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ABCA1	NM_005502.4	c.-93+6751T>C		intron_variant		ENST00000374736.8	NP_005493.2
LOC124902239	XR_007061706.1	n.1089-928A>G		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ABCA1	ENST00000374736.8	c.-93+6751T>C		intron_variant		1	NM_005502.4	ENSP00000363868	P1
ABCA1	ENST00000374733.1	c.-115+6751T>C		intron_variant		2		ENSP00000363865
ABCA1	ENST00000423487.6	c.-93+6751T>C		intron_variant		2		ENSP00000416623
ABCA1	ENST00000678995.1	c.-93+6751T>C		intron_variant				ENSP00000504612

Frequencies

GnomAD3 genomes AF: 0.144 AC: 21898 AN: 152056 Hom.: 2369 Cov.: 33

Gnomad AFR AF: 0.311

Gnomad AMI AF: 0.0912

Gnomad AMR AF: 0.111

Gnomad ASJ AF: 0.0282

Gnomad EAS AF: 0.00173

Gnomad SAS AF: 0.0573

Gnomad FIN AF: 0.0845

Gnomad MID AF: 0.0411

Gnomad NFE AF: 0.0847

Gnomad OTH AF: 0.106

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

GnomAD4 genome AF: 0.144 AC: 21956 AN: 152174 Hom.: 2387 Cov.: 33 AF XY: 0.141 AC XY: 10503 AN XY: 74426

Gnomad4 AFR AF: 0.311

Gnomad4 AMR AF: 0.111

Gnomad4 ASJ AF: 0.0282

Gnomad4 EAS AF: 0.00174

Gnomad4 SAS AF: 0.0566

Gnomad4 FIN AF: 0.0845

Gnomad4 NFE AF: 0.0847

Gnomad4 OTH AF: 0.104

Alfa AF: 0.111 Hom.: 239

Bravo AF: 0.154

Asia WGS AF: 0.0470 AC: 165 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	3.6
DANN	Benign	0.85

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: rs7035693; hg19: chr9-107683465;