rs10820738

chr9-104828835-T-C

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_005502.4(ABCA1):c.2115+81A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0667 in 1,419,262 control chromosomes in the GnomAD database, including 4,503 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.064 (489 hom., cov: 33)
  • Exomes 𝑓: 0.067 (4014 hom.)
• Consequence: ABCA1 NM_005502.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.238

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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BP6: Variant 9-104828835-T-C is Benign according to our data. Variant chr9-104828835-T-C is described in ClinVar as [Benign]. Clinvar id is 1280071.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr9-104828835-T-C is described in Lovd as [Benign].
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.272 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ABCA1	NM_005502.4	c.2115+81A>G		intron_variant		ENST00000374736.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ABCA1	ENST00000374736.8	c.2115+81A>G		intron_variant		1	NM_005502.4	P1
ABCA1	ENST00000678995.1	c.2115+81A>G		intron_variant
ABCA1	ENST00000494467.1	n.288+81A>G		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes AF: 0.0637 AC: 9685 AN: 152154 Hom.: 486 Cov.: 33

Gnomad AFR AF: 0.0296

Gnomad AMI AF: 0.0800

Gnomad AMR AF: 0.0978

Gnomad ASJ AF: 0.0991

Gnomad EAS AF: 0.284

Gnomad SAS AF: 0.0962

Gnomad FIN AF: 0.0466

Gnomad MID AF: 0.0886

Gnomad NFE AF: 0.0577

Gnomad OTH AF: 0.0785

GnomAD4 exome AF: 0.0670 AC: 84914 AN: 1266990 Hom.: 4014 AF XY: 0.0679 AC XY: 43119 AN XY: 634934

Gnomad4 AFR exome AF: 0.0275

Gnomad4 AMR exome AF: 0.123

Gnomad4 ASJ exome AF: 0.107

Gnomad4 EAS exome AF: 0.281

Gnomad4 SAS exome AF: 0.0913

Gnomad4 FIN exome AF: 0.0456

Gnomad4 NFE exome AF: 0.0553

Gnomad4 OTH exome AF: 0.0784

GnomAD4 genome AF: 0.0637 AC: 9703 AN: 152272 Hom.: 489 Cov.: 33 AF XY: 0.0663 AC XY: 4938 AN XY: 74460

Gnomad4 AFR AF: 0.0298

Gnomad4 AMR AF: 0.0981

Gnomad4 ASJ AF: 0.0991

Gnomad4 EAS AF: 0.284

Gnomad4 SAS AF: 0.0963

Gnomad4 FIN AF: 0.0466

Gnomad4 NFE AF: 0.0576

Gnomad4 OTH AF: 0.0839

Alfa AF: 0.0570 Hom.: 41

Bravo AF: 0.0699

Asia WGS AF: 0.163 AC: 567 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Oct 17, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
Cadd	Benign	3.4
Dann	Benign	0.44

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: rs10820738; hg19: chr9-107591116; COSMIC: COSV66068421;