chr9-104790643-A-G

Variant names:

• chr9-104790643-A-G
• rs4149333
• NM_005502.4:c.5927+279T>C

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 4 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 -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 VariationId is 1274636.Status of the report is criteria_provided_single_submitter, 1 stars.
• 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 rank	MANE	Protein	UniProt
ABCA1	NM_005502.4	c.5927+279T>C		intron_variant	Intron 44 of 49	ENST00000374736.8	NP_005493.2
NIPSNAP3B	XR_007061325.1	n.3986A>G		non_coding_transcript_exon_variant	Exon 7 of 7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ABCA1	ENST00000374736.8	c.5927+279T>C		intron_variant	Intron 44 of 49	1	NM_005502.4	ENSP00000363868.3
ABCA1	ENST00000678995.1	c.5933+279T>C		intron_variant	Intron 44 of 49			ENSP00000504612.1

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

African (AFR) AF: 0.475 AC: 19621 AN: 41324

American (AMR) AF: 0.155 AC: 2362 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.102 AC: 354 AN: 3470

East Asian (EAS) AF: 0.416 AC: 2139 AN: 5146

South Asian (SAS) AF: 0.223 AC: 1075 AN: 4818

European-Finnish (FIN) AF: 0.0590 AC: 626 AN: 10616

Middle Eastern (MID) AF: 0.272 AC: 80 AN: 294

European-Non Finnish (NFE) AF: 0.117 AC: 7927 AN: 68002

Other (OTH) AF: 0.207 AC: 437 AN: 2112

Alfa AF: 0.141 Hom.: 2626

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

Nov 07, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	1.0
DANN	Benign	0.79
PhyloP100		-0.59
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: rs4149333; hg19: chr9-107552924;