rs2575875

chr9-104900213-G-A

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.66+3401C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.455 in 151,952 control chromosomes in the GnomAD database, including 17,147 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.45 (17147 hom., cov: 31)
• Consequence: ABCA1 NM_005502.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.108

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=-0.81).
• BP6: Variant 9-104900213-G-A is Benign according to our data. Variant chr9-104900213-G-A is described in ClinVar as [Benign]. Clinvar id is 1262580.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.654 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ABCA1	NM_005502.4	c.66+3401C>T		intron_variant		ENST00000374736.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ABCA1	ENST00000374736.8	c.66+3401C>T		intron_variant		1	NM_005502.4	P1
ABCA1	ENST00000374733.1	c.-114-11018C>T		intron_variant		2
ABCA1	ENST00000423487.6	c.66+3401C>T		intron_variant		2
ABCA1	ENST00000678995.1	c.66+3401C>T		intron_variant

Frequencies

GnomAD3 genomes AF: 0.455 AC: 69024 AN: 151832 Hom.: 17096 Cov.: 31

Gnomad AFR AF: 0.660

Gnomad AMI AF: 0.491

Gnomad AMR AF: 0.394

Gnomad ASJ AF: 0.456

Gnomad EAS AF: 0.313

Gnomad SAS AF: 0.525

Gnomad FIN AF: 0.283

Gnomad MID AF: 0.510

Gnomad NFE AF: 0.375

Gnomad OTH AF: 0.461

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

GnomAD4 genome AF: 0.455 AC: 69132 AN: 151952 Hom.: 17147 Cov.: 31 AF XY: 0.449 AC XY: 33341 AN XY: 74240

Gnomad4 AFR AF: 0.661

Gnomad4 AMR AF: 0.394

Gnomad4 ASJ AF: 0.456

Gnomad4 EAS AF: 0.313

Gnomad4 SAS AF: 0.523

Gnomad4 FIN AF: 0.283

Gnomad4 NFE AF: 0.375

Gnomad4 OTH AF: 0.464

Alfa AF: 0.403 Hom.: 17039

Bravo AF: 0.470

Asia WGS AF: 0.460 AC: 1597 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 16, 2019

This variant is associated with the following publications: (PMID: 31039173) -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
Cadd	Benign	1.7
Dann	Benign	0.75

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: rs2575875; hg19: chr9-107662494; COSMIC: COSV66058124;