rs2740484

chr9-104788899-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.5928-332G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.266 in 152,162 control chromosomes in the GnomAD database, including 6,312 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in Lovd as Benign (no stars).

• Frequency: Genomes: 𝑓 0.27 (6312 hom., cov: 32)
• Consequence: ABCA1 NM_005502.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.51

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:):

ACMG classification

Verdict is Benign. Variant got -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BP6: Variant 9-104788899-C-T is Benign according to our data. Variant chr9-104788899-C-T is described in Lovd as [Benign].
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.346 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ABCA1	NM_005502.4	c.5928-332G>A		intron_variant		ENST00000374736.8
NIPSNAP3B	XR_007061325.1	n.2242C>T		non_coding_transcript_exon_variant	7/7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ABCA1	ENST00000374736.8	c.5928-332G>A		intron_variant		1	NM_005502.4	P1
ABCA1	ENST00000678995.1	c.5934-332G>A		intron_variant

Frequencies

GnomAD3 genomes AF: 0.266 AC: 40501 AN: 152044 Hom.: 6305 Cov.: 32

Gnomad AFR AF: 0.121

Gnomad AMI AF: 0.275

Gnomad AMR AF: 0.317

Gnomad ASJ AF: 0.311

Gnomad EAS AF: 0.0422

Gnomad SAS AF: 0.156

Gnomad FIN AF: 0.365

Gnomad MID AF: 0.244

Gnomad NFE AF: 0.350

Gnomad OTH AF: 0.284

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

GnomAD4 genome AF: 0.266 AC: 40532 AN: 152162 Hom.: 6312 Cov.: 32 AF XY: 0.265 AC XY: 19704 AN XY: 74386

Gnomad4 AFR AF: 0.122

Gnomad4 AMR AF: 0.317

Gnomad4 ASJ AF: 0.311

Gnomad4 EAS AF: 0.0421

Gnomad4 SAS AF: 0.157

Gnomad4 FIN AF: 0.365

Gnomad4 NFE AF: 0.350

Gnomad4 OTH AF: 0.281

Alfa AF: 0.324 Hom.: 5528

Bravo AF: 0.261

Asia WGS AF: 0.0990 AC: 348 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
Cadd	Benign	0.62
Dann	Benign	0.43

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: rs2740484; hg19: chr9-107551180;