rs4149333

chr9-104790643-A-G

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.5927+279T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.229 in 151,964 control chromosomes in the GnomAD database, including 5,946 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.23 (5946 hom., cov: 33)
• Consequence: ABCA1 NM_005502.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.590

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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BP6: Variant 9-104790643-A-G is Benign according to our data. Variant chr9-104790643-A-G is described in ClinVar as [Benign]. Clinvar id is 1274636.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr9-104790643-A-G is described in Lovd as [Benign].
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.469 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ABCA1	NM_005502.4	c.5927+279T>C		intron_variant		ENST00000374736.8
NIPSNAP3B	XR_007061325.1	n.3986A>G		non_coding_transcript_exon_variant	7/7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ABCA1	ENST00000374736.8	c.5927+279T>C		intron_variant		1	NM_005502.4	P1
ABCA1	ENST00000678995.1	c.5933+279T>C		intron_variant

Frequencies

GnomAD3 genomes AF: 0.229 AC: 34753 AN: 151846 Hom.: 5933 Cov.: 33

Gnomad AFR AF: 0.475

Gnomad AMI AF: 0.209

Gnomad AMR AF: 0.155

Gnomad ASJ AF: 0.102

Gnomad EAS AF: 0.416

Gnomad SAS AF: 0.223

Gnomad FIN AF: 0.0590

Gnomad MID AF: 0.275

Gnomad NFE AF: 0.117

Gnomad OTH AF: 0.206

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

GnomAD4 genome AF: 0.229 AC: 34811 AN: 151964 Hom.: 5946 Cov.: 33 AF XY: 0.224 AC XY: 16654 AN XY: 74324

Gnomad4 AFR AF: 0.475

Gnomad4 AMR AF: 0.155

Gnomad4 ASJ AF: 0.102

Gnomad4 EAS AF: 0.416

Gnomad4 SAS AF: 0.223

Gnomad4 FIN AF: 0.0590

Gnomad4 NFE AF: 0.117

Gnomad4 OTH AF: 0.207

Alfa AF: 0.137 Hom.: 1995

Bravo AF: 0.248

Asia WGS AF: 0.363 AC: 1253 AN: 3466

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

Nov 07, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
Cadd	Benign	1.0
Dann	Benign	0.79

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: rs4149333; hg19: chr9-107552924;