dbSNP rs2482432: NIPSNAP3B:n.960-6726T>C (chr9-104780891-T-C) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The XR_007061325.1(NIPSNAP3B):n.960-6726T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.365 in 152,436 control chromosomes in the GnomAD database, including 10,899 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.37 ( 10881 hom., cov: 32)

Exomes 𝑓: 0.37 ( 18 hom. )

Consequence

NIPSNAP3B
XR_007061325.1 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.0110

Publications

8 publications found

Variant links:

Genes affected

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:

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

ABCA1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.9).

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.444 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NIPSNAP3B	XR_007061325.1 link	n.960-6726T>C		intron_variant	Intron 6 of 6
ABCA1	NM_005502.4 link	c.*3424A>G		downstream_gene_variant		ENST00000374736.8	NP_005493.2	O95477B7XCW9B2RUU2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ABCA1	ENST00000374736.8 link	c.*3424A>G		downstream_gene_variant		1	NM_005502.4	ENSP00000363868.3		O95477
ABCA1	ENST00000678995.1 link	c.*3424A>G		downstream_gene_variant				ENSP00000504612.1		A0A7I2V5U0

Frequencies

GnomAD3 genomes

AF:

0.365

AC:

55529

AN:

151976

Hom.:

10878

Cov.:

show subpopulations

Gnomad AFR

AF:

0.245

Gnomad AMI

AF:

0.498

Gnomad AMR

AF:

0.393

Gnomad ASJ

AF:

0.532

Gnomad EAS

AF:

0.0972

Gnomad SAS

AF:

0.261

Gnomad FIN

AF:

0.370

Gnomad MID

AF:

0.364

Gnomad NFE

AF:

0.448

Gnomad OTH

AF:

0.400

GnomAD4 exome

AF:

0.368

AC:

125

AN:

340

Hom.:

AF XY:

0.384

AC XY:

AN XY:

216

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:

0.362

AC:

121

AN:

334

Middle Eastern (MID)

AC:

AN:

European-Non Finnish (NFE)

AF:

0.750

AC:

AN:

Other (OTH)

AF:

0.500

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.499

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.365

AC:

55551

AN:

152096

Hom.:

10881

Cov.:

AF XY:

0.360

AC XY:

26760

AN XY:

74354

show subpopulations

African (AFR)

AF:

0.245

AC:

10150

AN:

41486

American (AMR)

AF:

0.393

AC:

6010

AN:

15286

Ashkenazi Jewish (ASJ)

AF:

0.532

AC:

1846

AN:

3470

East Asian (EAS)

AF:

0.0971

AC:

503

AN:

5182

South Asian (SAS)

AF:

0.262

AC:

1264

AN:

4826

European-Finnish (FIN)

AF:

0.370

AC:

3912

AN:

10566

Middle Eastern (MID)

AF:

0.367

AC:

108

AN:

294

European-Non Finnish (NFE)

AF:

0.448

AC:

30470

AN:

67960

Other (OTH)

AF:

0.395

AC:

834

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

1753

3505

5258

7010

8763

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

530

1060

1590

2120

2650

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.422

Hom.:

19199

Bravo

AF:

0.365

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.90

CADD

Benign

0.73

(source)

DANN

Benign

0.73

PhyloP100

0.011

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over