NM_005502.4:c.5928-690G>A

Variant names:

• chr9-104789257-C-T
• rs2297406
• NM_005502.4:c.5928-690G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_005502.4(ABCA1):​c.5928-690G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.234 in 152,154 control chromosomes in the GnomAD database, including 5,255 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.23 (5255 hom., cov: 32)
• Consequence: ABCA1 NM_005502.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.467
• Publications: 12 publications found

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]

NIPSNAP3B (HGNC:23641): (nipsnap homolog 3B) NIPSNAP3B belongs to a family of proteins with putative roles in vesicular trafficking (Buechler et al., 2004 [PubMed 15177564]).[supplied by OMIM, Mar 2008]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.398 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_005502.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ABCA1	NM_005502.4	MANE Select	c.5928-690G>A		intron	N/A	NP_005493.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ABCA1	ENST00000374736.8	TSL:1 MANE Select	c.5928-690G>A		intron	N/A	ENSP00000363868.3
	ABCA1	ENST00000678995.1		c.5934-690G>A		intron	N/A	ENSP00000504612.1

Frequencies

GnomAD3 genomes AF: 0.235 AC: 35668 AN: 152036 Hom.: 5253 Cov.: 32

Gnomad AFR AF: 0.0558

Gnomad AMI AF: 0.399

Gnomad AMR AF: 0.206

Gnomad ASJ AF: 0.288

Gnomad EAS AF: 0.252

Gnomad SAS AF: 0.414

Gnomad FIN AF: 0.364

Gnomad MID AF: 0.218

Gnomad NFE AF: 0.311

Gnomad OTH AF: 0.220

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

GnomAD4 genome AF: 0.234 AC: 35672 AN: 152154 Hom.: 5255 Cov.: 32 AF XY: 0.241 AC XY: 17910 AN XY: 74382

African (AFR) AF: 0.0556 AC: 2311 AN: 41542

American (AMR) AF: 0.206 AC: 3145 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.288 AC: 1000 AN: 3472

East Asian (EAS) AF: 0.253 AC: 1306 AN: 5172

South Asian (SAS) AF: 0.413 AC: 1990 AN: 4818

European-Finnish (FIN) AF: 0.364 AC: 3847 AN: 10574

Middle Eastern (MID) AF: 0.214 AC: 63 AN: 294

European-Non Finnish (NFE) AF: 0.311 AC: 21175 AN: 67980

Other (OTH) AF: 0.223 AC: 471 AN: 2110

Alfa AF: 0.276 Hom.: 11874

Bravo AF: 0.209

Asia WGS AF: 0.307 AC: 1065 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	2.9
DANN	Benign	0.69
PhyloP100		-0.47
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs2297406; hg19: chr9-107551538;