Genetic Variant NM_005502.4:c.688C>A (chr9-104858554-G-T) – ACMG Classification: Likely_benign (-1 pts)

Variant summary

Our verdict is Likely benign. Variant got -1 ACMG points: 0P and 1B. BP4

The NM_005502.4(ABCA1):c.688C>A(p.Arg230Ser) variant causes a missense change. The variant allele was found at a frequency of 0.0000123 in 1,461,812 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R230C) has been classified as Likely benign.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.000012 ( 0 hom. )

Consequence

ABCA1
NM_005502.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 4.37

Variant links:

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 links:

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ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -1 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.27491334).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ABCA1	NM_005502.4 link	c.688C>A	p.Arg230Ser	missense_variant	Exon 7 of 50	ENST00000374736.8	NP_005493.2	O95477B7XCW9B2RUU2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
ABCA1	ENST00000374736.8 link	c.688C>A	p.Arg230Ser	missense_variant	Exon 7 of 50	1	NM_005502.4	ENSP00000363868.3	O95477
ABCA1	ENST00000678995.1 link	c.688C>A	p.Arg230Ser	missense_variant	Exon 7 of 50			ENSP00000504612.1	A0A7I2V5U0
ABCA1	ENST00000423487.6 link	c.688C>A	p.Arg230Ser	missense_variant	Exon 7 of 8	2		ENSP00000416623.2	B1AMI2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.0000123

AC:

AN:

1461812

Hom.:

Cov.:

AF XY:

0.0000151

AC XY:

AN XY:

727206

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000162

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.25

BayesDel_addAF

Uncertain

0.097

BayesDel_noAF

Benign

-0.10

CADD

Benign

DANN

Benign

0.93

DEOGEN2

Benign

0.25

T;T

Eigen

Benign

-0.16

Eigen_PC

Benign

0.0087

FATHMM_MKL

Uncertain

0.84

LIST_S2

Benign

0.66

T;T

M_CAP

Benign

0.065

MetaRNN

Benign

0.27

T;T

MetaSVM

Benign

-0.32

MutationAssessor

Benign

0.84

L;.

PrimateAI

Benign

0.22

PROVEAN

Benign

-0.31

N;N

REVEL

Uncertain

0.33

Sift

Benign

0.34

T;T

Sift4G

Benign

0.57

T;T

Polyphen

0.0

B;.

Vest4

0.27

MutPred

0.47

Loss of MoRF binding (P = 0.0068);Loss of MoRF binding (P = 0.0068);

MVP

0.95

MPC

0.20

ClinPred

0.58

GERP RS

5.1

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.22

gMVP

0.42

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

No publications associated with this variant yet.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over