9-104885374-G-A

Variant names:

• chr9-104885374-G-A
• rs3890182
• NM_005502.4:c.161-806C>T

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_Strong BP6 BA1

The NM_005502.4(ABCA1):​c.161-806C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.115 in 152,134 control chromosomes in the GnomAD database, including 1,081 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (no stars).

• Frequency: Genomes: 𝑓 0.12 (1081 hom., cov: 32)
• Consequence: ABCA1 NM_005502.4 intron
• Clinical Significance: Benign no assertion criteria provided B:1
• Conservation: PhyloP100: 0.173
• Publications: 83 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: Orphanet, Labcorp Genetics (formerly Invitae), G2P
• apolipoprotein A-I deficiency

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BP6: Variant 9-104885374-G-A is Benign according to our data. Variant chr9-104885374-G-A is described in ClinVar as Benign. ClinVar VariationId is 9507.Status of the report is no_assertion_criteria_provided, 0 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.12 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_005502.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ABCA1	NM_005502.4	MANE Select	c.161-806C>T		intron	N/A	NP_005493.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ABCA1	ENST00000374736.8	TSL:1 MANE Select	c.161-806C>T		intron	N/A	ENSP00000363868.3	O95477
	ABCA1	ENST00000678995.1		c.161-806C>T		intron	N/A	ENSP00000504612.1	A0A7I2V5U0
	ABCA1	ENST00000423487.6	TSL:2	c.161-806C>T		intron	N/A	ENSP00000416623.2	B1AMI2

Frequencies

GnomAD3 genomes AF: 0.116 AC: 17561 AN: 152016 Hom.: 1080 Cov.: 32

Gnomad AFR AF: 0.122

Gnomad AMI AF: 0.148

Gnomad AMR AF: 0.109

Gnomad ASJ AF: 0.105

Gnomad EAS AF: 0.0624

Gnomad SAS AF: 0.0914

Gnomad FIN AF: 0.101

Gnomad MID AF: 0.208

Gnomad NFE AF: 0.120

Gnomad OTH AF: 0.140

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.115 AC: 17571 AN: 152134 Hom.: 1081 Cov.: 32 AF XY: 0.113 AC XY: 8376 AN XY: 74368

African (AFR) AF: 0.122 AC: 5083 AN: 41498

American (AMR) AF: 0.109 AC: 1670 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.105 AC: 365 AN: 3470

East Asian (EAS) AF: 0.0625 AC: 324 AN: 5182

South Asian (SAS) AF: 0.0906 AC: 437 AN: 4822

European-Finnish (FIN) AF: 0.101 AC: 1073 AN: 10580

Middle Eastern (MID) AF: 0.200 AC: 58 AN: 290

European-Non Finnish (NFE) AF: 0.120 AC: 8128 AN: 67980

Other (OTH) AF: 0.141 AC: 298 AN: 2110

Alfa AF: 0.117 Hom.: 4367

Bravo AF: 0.117

Asia WGS AF: 0.111 AC: 387 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: no assertion criteria provided

Pathogenic	VUS	Benign	Condition
-	-	1	RECLASSIFIED - ABCA1 POLYMORPHISM (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	3.2
DANN	Benign	0.42
PhyloP100		0.17
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: rs3890182; hg19: chr9-107647655;