rs2275544

Positions:

• chr9-104888931-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.160+171A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.139 in 152,254 control chromosomes in the GnomAD database, including 1,562 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.14 (1562 hom., cov: 32)
• Consequence: ABCA1 NM_005502.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 1.56

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=-0.78).
• BP6: Variant 9-104888931-T-C is Benign according to our data. Variant chr9-104888931-T-C is described in ClinVar as [Benign]. Clinvar id is 1267812.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr9-104888931-T-C is described in Lovd as [Benign].
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.161 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ABCA1	NM_005502.4	c.160+171A>G		intron_variant		ENST00000374736.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ABCA1	ENST00000374736.8	c.160+171A>G		intron_variant		1	NM_005502.4	P1
ABCA1	ENST00000374733.1	c.-21+171A>G		intron_variant		2
ABCA1	ENST00000423487.6	c.160+171A>G		intron_variant		2
ABCA1	ENST00000678995.1	c.160+171A>G		intron_variant

Frequencies

GnomAD3 genomes AF: 0.139 AC: 21113 AN: 152136 Hom.: 1563 Cov.: 32

Gnomad AFR AF: 0.165

Gnomad AMI AF: 0.152

Gnomad AMR AF: 0.123

Gnomad ASJ AF: 0.113

Gnomad EAS AF: 0.0639

Gnomad SAS AF: 0.116

Gnomad FIN AF: 0.116

Gnomad MID AF: 0.231

Gnomad NFE AF: 0.138

Gnomad OTH AF: 0.161

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

GnomAD4 genome AF: 0.139 AC: 21136 AN: 152254 Hom.: 1562 Cov.: 32 AF XY: 0.135 AC XY: 10074 AN XY: 74456

Gnomad4 AFR AF: 0.165

Gnomad4 AMR AF: 0.123

Gnomad4 ASJ AF: 0.113

Gnomad4 EAS AF: 0.0640

Gnomad4 SAS AF: 0.116

Gnomad4 FIN AF: 0.116

Gnomad4 NFE AF: 0.138

Gnomad4 OTH AF: 0.161

Alfa AF: 0.140 Hom.: 447

Bravo AF: 0.140

Asia WGS AF: 0.124 AC: 432 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

Sep 29, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.78
CADD	Benign	13
DANN	Benign	0.85

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: rs2275544; hg19: chr9-107651212;