Genetic Variant NM_005502.4:c.*2897_*2899delGTT (chr9-104781415-TAAC-T) – ACMG Classification: Benign (-10 pts)

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP6_ModerateBA1

The NM_005502.4(ABCA1):c.*2897_*2899delGTT variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.111 in 152,524 control chromosomes in the GnomAD database, including 1,187 homozygotes. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.11 ( 1187 hom., cov: 31)

Exomes 𝑓: 0.060 ( 0 hom. )

Consequence

ABCA1
NM_005502.4 3_prime_UTR

Scores

Not classified

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 1.63

Publications

4 publications found

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:

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]

NIPSNAP3B links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -10 ACMG points.

BP6

Variant 9-104781415-TAAC-T is Benign according to our data. Variant chr9-104781415-TAAC-T is described in ClinVar as [Benign]. Clinvar id is 1287228.Status of the report is criteria_provided_single_submitter, 1 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.24 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ABCA1	NM_005502.4 link	c.2897_2899delGTT		3_prime_UTR_variant	Exon 50 of 50	ENST00000374736.8	NP_005493.2	O95477B7XCW9B2RUU2
NIPSNAP3B	XR_007061325.1 link	n.960-6199_960-6197delCAA		intron_variant	Intron 6 of 6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ABCA1	ENST00000374736.8 link	c.2897_2899delGTT		3_prime_UTR_variant	Exon 50 of 50	1	NM_005502.4	ENSP00000363868.3		O95477
ABCA1	ENST00000678995.1 link	c.2897_2899delGTT		3_prime_UTR_variant	Exon 50 of 50			ENSP00000504612.1		A0A7I2V5U0

Frequencies

GnomAD3 genomes

AF:

0.111

AC:

16904

AN:

151974

Hom.:

1183

Cov.:

show subpopulations

Gnomad AFR

AF:

0.145

Gnomad AMI

AF:

0.0263

Gnomad AMR

AF:

0.192

Gnomad ASJ

AF:

0.0726

Gnomad EAS

AF:

0.251

Gnomad SAS

AF:

0.0427

Gnomad FIN

AF:

0.0629

Gnomad MID

AF:

0.0854

Gnomad NFE

AF:

0.0775

Gnomad OTH

AF:

0.111

GnomAD4 exome

AF:

0.0602

AC:

AN:

432

Hom.:

AF XY:

0.0385

AC XY:

AN XY:

260

show subpopulations

African (AFR)

AC:

AN:

American (AMR)

AC:

AN:

Ashkenazi Jewish (ASJ)

AC:

AN:

East Asian (EAS)

AC:

AN:

South Asian (SAS)

AC:

AN:

European-Finnish (FIN)

AF:

0.0610

AC:

AN:

426

Middle Eastern (MID)

AC:

AN:

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

Other (OTH)

AF:

0.00

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.111

AC:

16936

AN:

152092

Hom.:

1187

Cov.:

AF XY:

0.112

AC XY:

8310

AN XY:

74352

show subpopulations

African (AFR)

AF:

0.145

AC:

6025

AN:

41480

American (AMR)

AF:

0.193

AC:

2944

AN:

15276

Ashkenazi Jewish (ASJ)

AF:

0.0726

AC:

252

AN:

3470

East Asian (EAS)

AF:

0.251

AC:

1298

AN:

5172

South Asian (SAS)

AF:

0.0425

AC:

205

AN:

4826

European-Finnish (FIN)

AF:

0.0629

AC:

667

AN:

10602

Middle Eastern (MID)

AF:

0.0850

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0775

AC:

5263

AN:

67950

Other (OTH)

AF:

0.110

AC:

233

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.494

Heterozygous variant carriers

751

1502

2253

3004

3755

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.101

Hom.:

110

Bravo

AF:

0.127

Asia WGS

AF:

0.143

AC:

497

AN:

3476

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

May 08, 2021

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

PhyloP100

1.6

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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NM_005502.4:c.2897_2899delGTT

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over