9-104793430-C-G

Position:

• chr9-104793430-C-G

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_005502.4(ABCA1):​c.5507-130G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.129 in 1,306,800 control chromosomes in the GnomAD database, including 15,260 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.18 (3290 hom., cov: 32)
  • Exomes 𝑓: 0.12 (11970 hom.)
• Consequence: ABCA1 NM_005502.4 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -3.07

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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BP6: Variant 9-104793430-C-G is Benign according to our data. Variant chr9-104793430-C-G is described in ClinVar as [Benign]. Clinvar id is 1231674.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr9-104793430-C-G is described in Lovd as [Benign].
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.402 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ABCA1	NM_005502.4	c.5507-130G>C		intron_variant		ENST00000374736.8	NP_005493.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ABCA1	ENST00000374736.8	c.5507-130G>C		intron_variant		1	NM_005502.4	ENSP00000363868	P1
ABCA1	ENST00000678995.1	c.5513-130G>C		intron_variant				ENSP00000504612

Frequencies

GnomAD3 genomes AF: 0.176 AC: 26756 AN: 151692 Hom.: 3287 Cov.: 32

Gnomad AFR AF: 0.327

Gnomad AMI AF: 0.190

Gnomad AMR AF: 0.128

Gnomad ASJ AF: 0.0669

Gnomad EAS AF: 0.417

Gnomad SAS AF: 0.220

Gnomad FIN AF: 0.0568

Gnomad MID AF: 0.225

Gnomad NFE AF: 0.0988

Gnomad OTH AF: 0.160

GnomAD4 exome AF: 0.123 AC: 141996 AN: 1154990 Hom.: 11970 AF XY: 0.125 AC XY: 72660 AN XY: 581778

Gnomad4 AFR exome AF: 0.339

Gnomad4 AMR exome AF: 0.123

Gnomad4 ASJ exome AF: 0.0648

Gnomad4 EAS exome AF: 0.401

Gnomad4 SAS exome AF: 0.208

Gnomad4 FIN exome AF: 0.0610

Gnomad4 NFE exome AF: 0.101

Gnomad4 OTH exome AF: 0.142

GnomAD4 genome AF: 0.176 AC: 26789 AN: 151810 Hom.: 3290 Cov.: 32 AF XY: 0.174 AC XY: 12890 AN XY: 74182

Gnomad4 AFR AF: 0.327

Gnomad4 AMR AF: 0.128

Gnomad4 ASJ AF: 0.0669

Gnomad4 EAS AF: 0.417

Gnomad4 SAS AF: 0.220

Gnomad4 FIN AF: 0.0568

Gnomad4 NFE AF: 0.0988

Gnomad4 OTH AF: 0.161

Alfa AF: 0.0509 Hom.: 61

Bravo AF: 0.188

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Nov 07, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	0.35
DANN	Benign	0.46

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs4149327; hg19: chr9-107555711;