XR_007061325.1:n.960-6726T>C

Variant names:

• chr9-104780891-T-C
• rs2482432
• XR_007061325.1:n.960-6726T>C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

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
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0110

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]

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]

ACMG classification

Verdict is Benign. Variant got -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	n.960-6726T>C		intron_variant	Intron 6 of 6
ABCA1	NM_005502.4	c.*3424A>G		downstream_gene_variant		ENST00000374736.8	NP_005493.2

Ensembl

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

Frequencies

GnomAD3 genomes AF: 0.365 AC: 55529 AN: 151976 Hom.: 10878 Cov.: 32

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.: 18 AF XY: 0.384 AC XY: 83 AN XY: 216

Gnomad4 FIN exome AF: 0.362

Gnomad4 NFE exome AF: 0.750

Gnomad4 OTH exome AF: 0.500

GnomAD4 genome AF: 0.365 AC: 55551 AN: 152096 Hom.: 10881 Cov.: 32 AF XY: 0.360 AC XY: 26760 AN XY: 74354

Gnomad4 AFR AF: 0.245

Gnomad4 AMR AF: 0.393

Gnomad4 ASJ AF: 0.532

Gnomad4 EAS AF: 0.0971

Gnomad4 SAS AF: 0.262

Gnomad4 FIN AF: 0.370

Gnomad4 NFE AF: 0.448

Gnomad4 OTH AF: 0.395

Alfa AF: 0.443 Hom.: 13079

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
DANN	Benign	0.73

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs2482432; hg19: chr9-107543172;