rs4149268

Positions:

• chr9-104884939-C-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.161-371G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.453 in 152,120 control chromosomes in the GnomAD database, including 17,250 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in Lovd as Benign (no stars).

• Frequency: Genomes: 𝑓 0.45 (17250 hom., cov: 33)
• Consequence: ABCA1 NM_005502.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.97

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=-0.89).
• BP6: Variant 9-104884939-C-T is Benign according to our data. Variant chr9-104884939-C-T is described in Lovd as [Benign].
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.663 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ABCA1	NM_005502.4	c.161-371G>A		intron_variant		ENST00000374736.8	NP_005493.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ABCA1	ENST00000374736.8	c.161-371G>A		intron_variant		1	NM_005502.4	ENSP00000363868.3
ABCA1	ENST00000678995.1	c.161-371G>A		intron_variant				ENSP00000504612.1
ABCA1	ENST00000423487.6	c.161-371G>A		intron_variant		2		ENSP00000416623.2
ABCA1	ENST00000374733.1	c.-20-371G>A		intron_variant		2		ENSP00000363865.1

Frequencies

GnomAD3 genomes AF: 0.453 AC: 68852 AN: 152002 Hom.: 17231 Cov.: 33

Gnomad AFR AF: 0.670

Gnomad AMI AF: 0.489

Gnomad AMR AF: 0.361

Gnomad ASJ AF: 0.444

Gnomad EAS AF: 0.318

Gnomad SAS AF: 0.542

Gnomad FIN AF: 0.282

Gnomad MID AF: 0.513

Gnomad NFE AF: 0.372

Gnomad OTH AF: 0.449

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

GnomAD4 genome AF: 0.453 AC: 68919 AN: 152120 Hom.: 17250 Cov.: 33 AF XY: 0.446 AC XY: 33193 AN XY: 74354

Gnomad4 AFR AF: 0.670

Gnomad4 AMR AF: 0.361

Gnomad4 ASJ AF: 0.444

Gnomad4 EAS AF: 0.318

Gnomad4 SAS AF: 0.541

Gnomad4 FIN AF: 0.282

Gnomad4 NFE AF: 0.372

Gnomad4 OTH AF: 0.453

Alfa AF: 0.391 Hom.: 26571

Bravo AF: 0.465

Asia WGS AF: 0.479 AC: 1664 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.035
DANN	Benign	0.77

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: rs4149268; hg19: chr9-107647220; COSMIC: COSV66058048;