rs2066882

Positions:

• chr9-104786181-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.6401+117A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.103 in 866,942 control chromosomes in the GnomAD database, including 7,061 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.11 (1216 hom., cov: 34)
  • Exomes 𝑓: 0.10 (5845 hom.)
• Consequence: ABCA1 NM_005502.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.916

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]

NIPSNAP3B (HGNC:):

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BP6: Variant 9-104786181-T-C is Benign according to our data. Variant chr9-104786181-T-C is described in ClinVar as [Benign]. Clinvar id is 1287036.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr9-104786181-T-C is described in Lovd as [Benign].
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.378 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ABCA1	NM_005502.4	c.6401+117A>G		intron_variant		ENST00000374736.8
NIPSNAP3B	XR_007061325.1	n.960-1436T>C		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ABCA1	ENST00000374736.8	c.6401+117A>G		intron_variant		1	NM_005502.4	P1
ABCA1	ENST00000678995.1	c.6407+117A>G		intron_variant

Frequencies

GnomAD3 genomes AF: 0.106 AC: 16121 AN: 152182 Hom.: 1210 Cov.: 34

Gnomad AFR AF: 0.138

Gnomad AMI AF: 0.0757

Gnomad AMR AF: 0.0676

Gnomad ASJ AF: 0.0878

Gnomad EAS AF: 0.393

Gnomad SAS AF: 0.215

Gnomad FIN AF: 0.0434

Gnomad MID AF: 0.0665

Gnomad NFE AF: 0.0769

Gnomad OTH AF: 0.100

GnomAD4 exome AF: 0.102 AC: 73093 AN: 714642 Hom.: 5845 AF XY: 0.106 AC XY: 40372 AN XY: 379646

Gnomad4 AFR exome AF: 0.140

Gnomad4 AMR exome AF: 0.0484

Gnomad4 ASJ exome AF: 0.0872

Gnomad4 EAS exome AF: 0.368

Gnomad4 SAS exome AF: 0.193

Gnomad4 FIN exome AF: 0.0437

Gnomad4 NFE exome AF: 0.0772

Gnomad4 OTH exome AF: 0.111

GnomAD4 genome AF: 0.106 AC: 16148 AN: 152300 Hom.: 1216 Cov.: 34 AF XY: 0.107 AC XY: 7935 AN XY: 74460

Gnomad4 AFR AF: 0.138

Gnomad4 AMR AF: 0.0675

Gnomad4 ASJ AF: 0.0878

Gnomad4 EAS AF: 0.393

Gnomad4 SAS AF: 0.214

Gnomad4 FIN AF: 0.0434

Gnomad4 NFE AF: 0.0769

Gnomad4 OTH AF: 0.102

Alfa AF: 0.0864 Hom.: 136

Bravo AF: 0.108

Asia WGS AF: 0.296 AC: 1025 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

Apr 07, 2019

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.23
DANN	Benign	0.54

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: rs2066882; hg19: chr9-107548462;