rs2066882

Variant names:

• chr9-104786181-T-C
• rs2066882
• NM_005502.4:c.6401+117A>G

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_005502.4(ABCA1):​c.6401+117A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.103 in 866,942 control chromosomes in the GnomAD database, including 7,061 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.11 (1216 hom., cov: 34)
  • Exomes 𝑓: 0.10 (5845 hom.)
• Consequence: ABCA1 NM_005502.4 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.916
• Publications: 10 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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BP6: Variant 9-104786181-T-C is Benign according to our data. Variant chr9-104786181-T-C is described in ClinVar as Benign. ClinVar VariationId is 1287036.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.378 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ABCA1	NM_005502.4	c.6401+117A>G		intron_variant	Intron 48 of 49	ENST00000374736.8	NP_005493.2
NIPSNAP3B	XR_007061325.1	n.960-1436T>C		intron_variant	Intron 6 of 6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ABCA1	ENST00000374736.8	c.6401+117A>G		intron_variant	Intron 48 of 49	1	NM_005502.4	ENSP00000363868.3
ABCA1	ENST00000678995.1	c.6407+117A>G		intron_variant	Intron 48 of 49			ENSP00000504612.1

Frequencies

GnomAD3 genomes AF: 0.106 AC: 16121 AN: 152182 Hom.: 1210 Cov.: 34

Gnomad AFR AF: 0.138

Gnomad AMI AF: 0.0757

Gnomad AMR AF: 0.0676

Gnomad ASJ AF: 0.0878

Gnomad EAS AF: 0.393

Gnomad SAS AF: 0.215

Gnomad FIN AF: 0.0434

Gnomad MID AF: 0.0665

Gnomad NFE AF: 0.0769

Gnomad OTH AF: 0.100

GnomAD4 exome AF: 0.102 AC: 73093 AN: 714642 Hom.: 5845 AF XY: 0.106 AC XY: 40372 AN XY: 379646

African (AFR) AF: 0.140 AC: 2608 AN: 18624

American (AMR) AF: 0.0484 AC: 1818 AN: 37530

Ashkenazi Jewish (ASJ) AF: 0.0872 AC: 1806 AN: 20720

East Asian (EAS) AF: 0.368 AC: 12545 AN: 34124

South Asian (SAS) AF: 0.193 AC: 12887 AN: 66770

European-Finnish (FIN) AF: 0.0437 AC: 1644 AN: 37606

Middle Eastern (MID) AF: 0.0855 AC: 351 AN: 4104

European-Non Finnish (NFE) AF: 0.0772 AC: 35451 AN: 459346

Other (OTH) AF: 0.111 AC: 3983 AN: 35818

GnomAD4 genome AF: 0.106 AC: 16148 AN: 152300 Hom.: 1216 Cov.: 34 AF XY: 0.107 AC XY: 7935 AN XY: 74460

African (AFR) AF: 0.138 AC: 5744 AN: 41554

American (AMR) AF: 0.0675 AC: 1032 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.0878 AC: 305 AN: 3472

East Asian (EAS) AF: 0.393 AC: 2035 AN: 5182

South Asian (SAS) AF: 0.214 AC: 1035 AN: 4828

European-Finnish (FIN) AF: 0.0434 AC: 461 AN: 10614

Middle Eastern (MID) AF: 0.0646 AC: 19 AN: 294

European-Non Finnish (NFE) AF: 0.0769 AC: 5232 AN: 68036

Other (OTH) AF: 0.102 AC: 216 AN: 2112

Alfa AF: 0.0918 Hom.: 1391

Bravo AF: 0.108

Asia WGS AF: 0.296 AC: 1025 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Apr 07, 2019

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	-0.89
CADD	Benign	0.23
DANN	Benign	0.54
PhyloP100		-0.92
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: rs2066882; hg19: chr9-107548462;