rs2249891

Positions:

• chr9-104861961-A-G

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.422-161T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.275 in 151,704 control chromosomes in the GnomAD database, including 9,074 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.27 (9074 hom., cov: 30)
• Consequence: ABCA1 NM_005502.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.0520

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=-0.84).
• BP6: Variant 9-104861961-A-G is Benign according to our data. Variant chr9-104861961-A-G is described in ClinVar as [Benign]. Clinvar id is 1229375.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr9-104861961-A-G is described in Lovd as [Benign].
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.593 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ABCA1	NM_005502.4	c.422-161T>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.422-161T>C		intron_variant		1	NM_005502.4	ENSP00000363868	P1
ABCA1	ENST00000374733.1	c.242-161T>C		intron_variant		2		ENSP00000363865
ABCA1	ENST00000423487.6	c.422-161T>C		intron_variant		2		ENSP00000416623
ABCA1	ENST00000678995.1	c.422-161T>C		intron_variant				ENSP00000504612

Frequencies

GnomAD3 genomes AF: 0.274 AC: 41595 AN: 151586 Hom.: 9048 Cov.: 30

Gnomad AFR AF: 0.599

Gnomad AMI AF: 0.175

Gnomad AMR AF: 0.264

Gnomad ASJ AF: 0.175

Gnomad EAS AF: 0.322

Gnomad SAS AF: 0.240

Gnomad FIN AF: 0.0809

Gnomad MID AF: 0.275

Gnomad NFE AF: 0.116

Gnomad OTH AF: 0.275

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

GnomAD4 genome AF: 0.275 AC: 41677 AN: 151704 Hom.: 9074 Cov.: 30 AF XY: 0.273 AC XY: 20195 AN XY: 74104

Gnomad4 AFR AF: 0.599

Gnomad4 AMR AF: 0.264

Gnomad4 ASJ AF: 0.175

Gnomad4 EAS AF: 0.323

Gnomad4 SAS AF: 0.240

Gnomad4 FIN AF: 0.0809

Gnomad4 NFE AF: 0.116

Gnomad4 OTH AF: 0.278

Alfa AF: 0.155 Hom.: 3355

Bravo AF: 0.304

Asia WGS AF: 0.296 AC: 1028 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

Aug 30, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	4.1
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: rs2249891; hg19: chr9-107624242; COSMIC: COSV66059377;