rs1331924

Positions:

• chr9-104785341-C-G
• chr9-104785341-C-T

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_005502.4(ABCA1):​c.6645+55G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.154 in 1,607,818 control chromosomes in the GnomAD database, including 23,192 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.21 (4470 hom., cov: 32)
  • Exomes 𝑓: 0.15 (18722 hom.)
• Consequence: ABCA1 NM_005502.4 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -3.29

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]

NIPSNAP3B (HGNC:):

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BP6: Variant 9-104785341-C-G is Benign according to our data. Variant chr9-104785341-C-G is described in ClinVar as [Benign]. Clinvar id is 1225848.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr9-104785341-C-G is described in Lovd as [Benign].
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.371 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ABCA1	NM_005502.4	c.6645+55G>C		intron_variant		ENST00000374736.8	NP_005493.2
NIPSNAP3B	XR_007061325.1	n.960-2276C>G		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ABCA1	ENST00000374736.8	c.6645+55G>C		intron_variant		1	NM_005502.4	ENSP00000363868	P1
ABCA1	ENST00000678995.1	c.6651+55G>C		intron_variant				ENSP00000504612

Frequencies

GnomAD3 genomes AF: 0.213 AC: 32410 AN: 151910 Hom.: 4449 Cov.: 32

Gnomad AFR AF: 0.376

Gnomad AMI AF: 0.0669

Gnomad AMR AF: 0.270

Gnomad ASJ AF: 0.147

Gnomad EAS AF: 0.283

Gnomad SAS AF: 0.0759

Gnomad FIN AF: 0.0794

Gnomad MID AF: 0.133

Gnomad NFE AF: 0.133

Gnomad OTH AF: 0.204

GnomAD4 exome AF: 0.148 AC: 215704 AN: 1455790 Hom.: 18722 AF XY: 0.144 AC XY: 104358 AN XY: 724322

Gnomad4 AFR exome AF: 0.381

Gnomad4 AMR exome AF: 0.313

Gnomad4 ASJ exome AF: 0.162

Gnomad4 EAS exome AF: 0.301

Gnomad4 SAS exome AF: 0.0782

Gnomad4 FIN exome AF: 0.0855

Gnomad4 NFE exome AF: 0.137

Gnomad4 OTH exome AF: 0.155

GnomAD4 genome AF: 0.214 AC: 32478 AN: 152028 Hom.: 4470 Cov.: 32 AF XY: 0.210 AC XY: 15640 AN XY: 74324

Gnomad4 AFR AF: 0.376

Gnomad4 AMR AF: 0.271

Gnomad4 ASJ AF: 0.147

Gnomad4 EAS AF: 0.283

Gnomad4 SAS AF: 0.0752

Gnomad4 FIN AF: 0.0794

Gnomad4 NFE AF: 0.133

Gnomad4 OTH AF: 0.205

Alfa AF: 0.0721 Hom.: 91

Bravo AF: 0.238

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Apr 12, 2019	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.13
DANN	Benign	0.52

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

LitVar

Other links and lift over

dbSNP: rs1331924; hg19: chr9-107547622; COSMIC: COSV66064007;