9-104827286-C-T

Variant names:

• chr9-104827286-C-T
• rs7024300
• NM_005502.4:c.2116-117G>A

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.2116-117G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0444 in 855,068 control chromosomes in the GnomAD database, including 1,331 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.058 (348 hom., cov: 32)
  • Exomes 𝑓: 0.041 (983 hom.)
• Consequence: ABCA1 NM_005502.4 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.813
• Publications: 6 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]

ABCA1 Gene-Disease associations (from GenCC):

• hypoalphalipoproteinemia, primary, 1

  Inheritance: AD Classification: DEFINITIVE, LIMITED Submitted by: Ambry Genetics, Labcorp Genetics (formerly Invitae)
• Tangier disease

  Inheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Labcorp Genetics (formerly Invitae), G2P, Orphanet
• apolipoprotein A-I deficiency

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).
• BP6: Variant 9-104827286-C-T is Benign according to our data. Variant chr9-104827286-C-T is described in ClinVar as Benign. ClinVar VariationId is 1235958.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.105 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ABCA1	NM_005502.4	c.2116-117G>A		intron_variant	Intron 15 of 49	ENST00000374736.8	NP_005493.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ABCA1	ENST00000374736.8	c.2116-117G>A		intron_variant	Intron 15 of 49	1	NM_005502.4	ENSP00000363868.3
ABCA1	ENST00000678995.1	c.2116-117G>A		intron_variant	Intron 15 of 49			ENSP00000504612.1
ABCA1	ENST00000494467.1	n.289-117G>A		intron_variant	Intron 2 of 3	3

Frequencies

GnomAD3 genomes AF: 0.0581 AC: 8834 AN: 152146 Hom.: 349 Cov.: 32

Gnomad AFR AF: 0.0948

Gnomad AMI AF: 0.155

Gnomad AMR AF: 0.109

Gnomad ASJ AF: 0.0533

Gnomad EAS AF: 0.0269

Gnomad SAS AF: 0.0627

Gnomad FIN AF: 0.0136

Gnomad MID AF: 0.108

Gnomad NFE AF: 0.0315

Gnomad OTH AF: 0.0688

GnomAD4 exome AF: 0.0415 AC: 29151 AN: 702804 Hom.: 983 AF XY: 0.0418 AC XY: 15464 AN XY: 369818

African (AFR) AF: 0.0856 AC: 1575 AN: 18410

American (AMR) AF: 0.135 AC: 4703 AN: 34814

Ashkenazi Jewish (ASJ) AF: 0.0490 AC: 1017 AN: 20744

East Asian (EAS) AF: 0.0465 AC: 1513 AN: 32560

South Asian (SAS) AF: 0.0638 AC: 4141 AN: 64890

European-Finnish (FIN) AF: 0.0169 AC: 686 AN: 40528

Middle Eastern (MID) AF: 0.0904 AC: 276 AN: 3052

European-Non Finnish (NFE) AF: 0.0299 AC: 13547 AN: 452526

Other (OTH) AF: 0.0480 AC: 1693 AN: 35280

GnomAD4 genome AF: 0.0581 AC: 8845 AN: 152264 Hom.: 348 Cov.: 32 AF XY: 0.0586 AC XY: 4365 AN XY: 74450

African (AFR) AF: 0.0947 AC: 3935 AN: 41546

American (AMR) AF: 0.109 AC: 1673 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.0533 AC: 185 AN: 3472

East Asian (EAS) AF: 0.0272 AC: 141 AN: 5188

South Asian (SAS) AF: 0.0625 AC: 302 AN: 4830

European-Finnish (FIN) AF: 0.0136 AC: 144 AN: 10604

Middle Eastern (MID) AF: 0.106 AC: 31 AN: 292

European-Non Finnish (NFE) AF: 0.0316 AC: 2147 AN: 68020

Other (OTH) AF: 0.0690 AC: 146 AN: 2116

Alfa AF: 0.0525 Hom.: 42

Bravo AF: 0.0660

Asia WGS AF: 0.0670 AC: 231 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

- -

Aug 30, 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	-0.93
CADD	Benign	0.30
DANN	Benign	0.39
PhyloP100		-0.81
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: rs7024300; hg19: chr9-107589567;