NM_005502.4:c.5507-130G>C

Variant names:

• chr9-104793430-C-G
• rs4149327
• NM_005502.4:c.5507-130G>C

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.5507-130G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.129 in 1,306,800 control chromosomes in the GnomAD database, including 15,260 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.18 (3290 hom., cov: 32)
  • Exomes 𝑓: 0.12 (11970 hom.)
• Consequence: ABCA1 NM_005502.4 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -3.07
• 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]

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=-0.86).
• BP6: Variant 9-104793430-C-G is Benign according to our data. Variant chr9-104793430-C-G is described in ClinVar as Benign. ClinVar VariationId is 1231674.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.402 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ABCA1	NM_005502.4	c.5507-130G>C		intron_variant	Intron 40 of 49	ENST00000374736.8	NP_005493.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ABCA1	ENST00000374736.8	c.5507-130G>C		intron_variant	Intron 40 of 49	1	NM_005502.4	ENSP00000363868.3
ABCA1	ENST00000678995.1	c.5513-130G>C		intron_variant	Intron 40 of 49			ENSP00000504612.1

Frequencies

GnomAD3 genomes AF: 0.176 AC: 26756 AN: 151692 Hom.: 3287 Cov.: 32

Gnomad AFR AF: 0.327

Gnomad AMI AF: 0.190

Gnomad AMR AF: 0.128

Gnomad ASJ AF: 0.0669

Gnomad EAS AF: 0.417

Gnomad SAS AF: 0.220

Gnomad FIN AF: 0.0568

Gnomad MID AF: 0.225

Gnomad NFE AF: 0.0988

Gnomad OTH AF: 0.160

GnomAD4 exome AF: 0.123 AC: 141996 AN: 1154990 Hom.: 11970 AF XY: 0.125 AC XY: 72660 AN XY: 581778

African (AFR) AF: 0.339 AC: 8939 AN: 26370

American (AMR) AF: 0.123 AC: 4265 AN: 34644

Ashkenazi Jewish (ASJ) AF: 0.0648 AC: 1518 AN: 23422

East Asian (EAS) AF: 0.401 AC: 14234 AN: 35510

South Asian (SAS) AF: 0.208 AC: 15405 AN: 74134

European-Finnish (FIN) AF: 0.0610 AC: 2561 AN: 42008

Middle Eastern (MID) AF: 0.168 AC: 865 AN: 5148

European-Non Finnish (NFE) AF: 0.101 AC: 87082 AN: 863646

Other (OTH) AF: 0.142 AC: 7127 AN: 50108

GnomAD4 genome AF: 0.176 AC: 26789 AN: 151810 Hom.: 3290 Cov.: 32 AF XY: 0.174 AC XY: 12890 AN XY: 74182

African (AFR) AF: 0.327 AC: 13514 AN: 41378

American (AMR) AF: 0.128 AC: 1948 AN: 15268

Ashkenazi Jewish (ASJ) AF: 0.0669 AC: 232 AN: 3466

East Asian (EAS) AF: 0.417 AC: 2151 AN: 5164

South Asian (SAS) AF: 0.220 AC: 1058 AN: 4814

European-Finnish (FIN) AF: 0.0568 AC: 595 AN: 10476

Middle Eastern (MID) AF: 0.221 AC: 65 AN: 294

European-Non Finnish (NFE) AF: 0.0988 AC: 6714 AN: 67926

Other (OTH) AF: 0.161 AC: 339 AN: 2112

Alfa AF: 0.0509 Hom.: 61

Bravo AF: 0.188

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

- -

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	-0.86
CADD	Benign	0.35
DANN	Benign	0.46
PhyloP100		-3.1
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs4149327; hg19: chr9-107555711;