rs3890182

Positions:

• chr9-104885374-G-A
• chr9-104885374-G-T

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_Strong BP6 BA1

The NM_005502.4(ABCA1):​c.161-806C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.115 in 152,134 control chromosomes in the GnomAD database, including 1,081 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (no stars).

• Frequency: Genomes: 𝑓 0.12 (1081 hom., cov: 32)
• Consequence: ABCA1 NM_005502.4 intron
• Clinical Significance: Benign no assertion criteria provided B:1
• Conservation: PhyloP100: 0.173

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 -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BP6: Variant 9-104885374-G-A is Benign according to our data. Variant chr9-104885374-G-A is described in ClinVar as [Benign]. Clinvar id is 9507.Status of the report is no_assertion_criteria_provided, 0 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.12 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ABCA1	NM_005502.4	c.161-806C>T		intron_variant		ENST00000374736.8	NP_005493.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ABCA1	ENST00000374736.8	c.161-806C>T		intron_variant		1	NM_005502.4	ENSP00000363868	P1
ABCA1	ENST00000374733.1	c.-20-806C>T		intron_variant		2		ENSP00000363865
ABCA1	ENST00000423487.6	c.161-806C>T		intron_variant		2		ENSP00000416623
ABCA1	ENST00000678995.1	c.161-806C>T		intron_variant				ENSP00000504612

Frequencies

GnomAD3 genomes AF: 0.116 AC: 17561 AN: 152016 Hom.: 1080 Cov.: 32

Gnomad AFR AF: 0.122

Gnomad AMI AF: 0.148

Gnomad AMR AF: 0.109

Gnomad ASJ AF: 0.105

Gnomad EAS AF: 0.0624

Gnomad SAS AF: 0.0914

Gnomad FIN AF: 0.101

Gnomad MID AF: 0.208

Gnomad NFE AF: 0.120

Gnomad OTH AF: 0.140

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

GnomAD4 genome AF: 0.115 AC: 17571 AN: 152134 Hom.: 1081 Cov.: 32 AF XY: 0.113 AC XY: 8376 AN XY: 74368

Gnomad4 AFR AF: 0.122

Gnomad4 AMR AF: 0.109

Gnomad4 ASJ AF: 0.105

Gnomad4 EAS AF: 0.0625

Gnomad4 SAS AF: 0.0906

Gnomad4 FIN AF: 0.101

Gnomad4 NFE AF: 0.120

Gnomad4 OTH AF: 0.141

Alfa AF: 0.115 Hom.: 1971

Bravo AF: 0.117

Asia WGS AF: 0.111 AC: 387 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

Submissions by phenotype

ABCA1 polymorphism Benign:1

Benign, no assertion criteria provided

literature only

OMIM

Mar 20, 2008

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	3.2
DANN	Benign	0.42

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: rs3890182; hg19: chr9-107647655;