rs1331924

Variant names:

• chr9-104785341-C-G
• rs1331924
• NM_005502.4:c.6645+55G>C

Your query was ambiguous. Multiple possible variants found:

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

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 13 publications found

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: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]

ACMG classification

Our verdict: Benign. The variant received -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 VariationId is 1225848.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• 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 rank	MANE	Protein	UniProt
ABCA1	NM_005502.4	c.6645+55G>C		intron_variant	Intron 49 of 49	ENST00000374736.8	NP_005493.2
NIPSNAP3B	XR_007061325.1	n.960-2276C>G		intron_variant	Intron 6 of 6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ABCA1	ENST00000374736.8	c.6645+55G>C		intron_variant	Intron 49 of 49	1	NM_005502.4	ENSP00000363868.3
ABCA1	ENST00000678995.1	c.6651+55G>C		intron_variant	Intron 49 of 49			ENSP00000504612.1

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

African (AFR) AF: 0.381 AC: 12720 AN: 33398

American (AMR) AF: 0.313 AC: 13944 AN: 44510

Ashkenazi Jewish (ASJ) AF: 0.162 AC: 4235 AN: 26084

East Asian (EAS) AF: 0.301 AC: 11918 AN: 39590

South Asian (SAS) AF: 0.0782 AC: 6700 AN: 85630

European-Finnish (FIN) AF: 0.0855 AC: 4413 AN: 51598

Middle Eastern (MID) AF: 0.123 AC: 677 AN: 5484

European-Non Finnish (NFE) AF: 0.137 AC: 151787 AN: 1109314

Other (OTH) AF: 0.155 AC: 9310 AN: 60182

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

African (AFR) AF: 0.376 AC: 15575 AN: 41430

American (AMR) AF: 0.271 AC: 4140 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.147 AC: 510 AN: 3470

East Asian (EAS) AF: 0.283 AC: 1457 AN: 5148

South Asian (SAS) AF: 0.0752 AC: 362 AN: 4816

European-Finnish (FIN) AF: 0.0794 AC: 841 AN: 10596

Middle Eastern (MID) AF: 0.139 AC: 41 AN: 294

European-Non Finnish (NFE) AF: 0.133 AC: 9058 AN: 67966

Other (OTH) AF: 0.205 AC: 433 AN: 2112

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

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Apr 12, 2019

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.13
DANN	Benign	0.52
PhyloP100		-3.3
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

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