9-104790904-A-G

Variant names:

• chr9-104790904-A-G
• rs2020927
• NM_005502.4:c.5927+18T>C

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.5927+18T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.158 in 1,519,884 control chromosomes in the GnomAD database, including 26,755 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.24 (6611 hom., cov: 32)
  • Exomes 𝑓: 0.15 (20144 hom.)
• Consequence: ABCA1 NM_005502.4 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:5
• Conservation: PhyloP100: 0.276
• Publications: 18 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=-0.87).
• BP6: Variant 9-104790904-A-G is Benign according to our data. Variant chr9-104790904-A-G is described in ClinVar as Benign. ClinVar VariationId is 928662.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.495 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_005502.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ABCA1	NM_005502.4	MANE Select	c.5927+18T>C		intron	N/A	NP_005493.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ABCA1	ENST00000374736.8	TSL:1 MANE Select	c.5927+18T>C		intron	N/A	ENSP00000363868.3
	ABCA1	ENST00000678995.1		c.5933+18T>C		intron	N/A	ENSP00000504612.1

Frequencies

GnomAD3 genomes AF: 0.241 AC: 36635 AN: 152004 Hom.: 6600 Cov.: 32

Gnomad AFR AF: 0.501

Gnomad AMI AF: 0.211

Gnomad AMR AF: 0.163

Gnomad ASJ AF: 0.120

Gnomad EAS AF: 0.419

Gnomad SAS AF: 0.227

Gnomad FIN AF: 0.0620

Gnomad MID AF: 0.313

Gnomad NFE AF: 0.123

Gnomad OTH AF: 0.223

GnomAD2 exomes AF: 0.182 AC: 45660 AN: 250776 AF XY: 0.177

Gnomad AFR exome AF: 0.513

Gnomad AMR exome AF: 0.148

Gnomad ASJ exome AF: 0.113

Gnomad EAS exome AF: 0.428

Gnomad FIN exome AF: 0.0652

Gnomad NFE exome AF: 0.125

Gnomad OTH exome AF: 0.159

GnomAD4 exome AF: 0.149 AC: 203445 AN: 1367762 Hom.: 20144 Cov.: 20 AF XY: 0.149 AC XY: 102375 AN XY: 686210

African (AFR) AF: 0.520 AC: 16374 AN: 31464

American (AMR) AF: 0.149 AC: 6642 AN: 44562

Ashkenazi Jewish (ASJ) AF: 0.115 AC: 2949 AN: 25554

East Asian (EAS) AF: 0.413 AC: 16138 AN: 39122

South Asian (SAS) AF: 0.215 AC: 18093 AN: 84156

European-Finnish (FIN) AF: 0.0677 AC: 3598 AN: 53140

Middle Eastern (MID) AF: 0.239 AC: 1334 AN: 5574

European-Non Finnish (NFE) AF: 0.125 AC: 128155 AN: 1026886

Other (OTH) AF: 0.177 AC: 10162 AN: 57304

GnomAD4 genome AF: 0.241 AC: 36690 AN: 152122 Hom.: 6611 Cov.: 32 AF XY: 0.236 AC XY: 17516 AN XY: 74372

African (AFR) AF: 0.501 AC: 20770 AN: 41440

American (AMR) AF: 0.163 AC: 2497 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.120 AC: 417 AN: 3470

East Asian (EAS) AF: 0.419 AC: 2166 AN: 5172

South Asian (SAS) AF: 0.226 AC: 1092 AN: 4826

European-Finnish (FIN) AF: 0.0620 AC: 657 AN: 10600

Middle Eastern (MID) AF: 0.306 AC: 90 AN: 294

European-Non Finnish (NFE) AF: 0.123 AC: 8337 AN: 68006

Other (OTH) AF: 0.223 AC: 472 AN: 2114

Alfa AF: 0.149 Hom.: 3286

Bravo AF: 0.260

Asia WGS AF: 0.366 AC: 1265 AN: 3472

ClinVar

Significance: Benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:3

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Oct 01, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

not specified Benign:1

Aug 12, 2019

Women's Health and Genetics/Laboratory Corporation of America, LabCorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Tangier disease Benign:1

Jul 14, 2021

Genome-Nilou Lab

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	6.4
DANN	Benign	0.61
PhyloP100		0.28
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: rs2020927; hg19: chr9-107553185; COSMIC: COSV66067802;