rs2020927

Positions:

• chr9-104790904-A-G

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_005502.4(ABCA1):​c.5927+18T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.158 in 1,519,884 control chromosomes in the GnomAD database, including 26,755 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.24 (6611 hom., cov: 32)
  • Exomes 𝑓: 0.15 (20144 hom.)
• Consequence: ABCA1 NM_005502.4 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:5
• Conservation: PhyloP100: 0.276

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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BP6: Variant 9-104790904-A-G is Benign according to our data. Variant chr9-104790904-A-G is described in ClinVar as [Benign]. Clinvar id is 928662.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr9-104790904-A-G is described in Lovd as [Benign].
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.495 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ABCA1	NM_005502.4	c.5927+18T>C		intron_variant		ENST00000374736.8	NP_005493.2
NIPSNAP3B	XR_007061325.1	n.*5A>G		downstream_gene_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ABCA1	ENST00000374736.8	c.5927+18T>C		intron_variant		1	NM_005502.4	ENSP00000363868.3
ABCA1	ENST00000678995.1	c.5933+18T>C		intron_variant				ENSP00000504612.1

Frequencies

GnomAD3 genomes AF: 0.241 AC: 36635 AN: 152004 Hom.: 6600 Cov.: 32

Gnomad AFR AF: 0.501

Gnomad AMI AF: 0.211

Gnomad AMR AF: 0.163

Gnomad ASJ AF: 0.120

Gnomad EAS AF: 0.419

Gnomad SAS AF: 0.227

Gnomad FIN AF: 0.0620

Gnomad MID AF: 0.313

Gnomad NFE AF: 0.123

Gnomad OTH AF: 0.223

GnomAD3 exomes AF: 0.182 AC: 45660 AN: 250776 Hom.: 6149 AF XY: 0.177 AC XY: 24038 AN XY: 135556

Gnomad AFR exome AF: 0.513

Gnomad AMR exome AF: 0.148

Gnomad ASJ exome AF: 0.113

Gnomad EAS exome AF: 0.428

Gnomad SAS exome AF: 0.218

Gnomad FIN exome AF: 0.0652

Gnomad NFE exome AF: 0.125

Gnomad OTH exome AF: 0.159

GnomAD4 exome AF: 0.149 AC: 203445 AN: 1367762 Hom.: 20144 Cov.: 20 AF XY: 0.149 AC XY: 102375 AN XY: 686210

Gnomad4 AFR exome AF: 0.520

Gnomad4 AMR exome AF: 0.149

Gnomad4 ASJ exome AF: 0.115

Gnomad4 EAS exome AF: 0.413

Gnomad4 SAS exome AF: 0.215

Gnomad4 FIN exome AF: 0.0677

Gnomad4 NFE exome AF: 0.125

Gnomad4 OTH exome AF: 0.177

GnomAD4 genome AF: 0.241 AC: 36690 AN: 152122 Hom.: 6611 Cov.: 32 AF XY: 0.236 AC XY: 17516 AN XY: 74372

Gnomad4 AFR AF: 0.501

Gnomad4 AMR AF: 0.163

Gnomad4 ASJ AF: 0.120

Gnomad4 EAS AF: 0.419

Gnomad4 SAS AF: 0.226

Gnomad4 FIN AF: 0.0620

Gnomad4 NFE AF: 0.123

Gnomad4 OTH AF: 0.223

Alfa AF: 0.145 Hom.: 2636

Bravo AF: 0.260

Asia WGS AF: 0.366 AC: 1265 AN: 3472

ClinVar

Significance: Benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:3

Benign, criteria provided, single submitter	clinical testing	GeneDx	Oct 01, 2018	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 31, 2024	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

not specified Benign:1

Benign, criteria provided, single submitter

clinical testing

Women's Health and Genetics/Laboratory Corporation of America, LabCorp

Aug 12, 2019

- -

Tangier disease Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Jul 14, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	6.4
DANN	Benign	0.61

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: rs2020927; hg19: chr9-107553185; COSMIC: COSV66067802;