rs363717

Variant names:

• chr9-104782419-C-T
• rs363717
• NM_005502.4:c.*1896G>A

Your query was ambiguous. Multiple possible variants found:

• chr9-104782419-C-T
• chr9-104782419-C-G

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.*1896G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.85 in 152,046 control chromosomes in the GnomAD database, including 55,237 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.85 (55237 hom., cov: 32)
  • Failed GnomAD Quality Control
• Consequence: ABCA1 NM_005502.4 3_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:4
• Conservation: PhyloP100: 0.0520
• Publications: 27 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=-0.9).
• BP6: Variant 9-104782419-C-T is Benign according to our data. Variant chr9-104782419-C-T is described in ClinVar as Benign. ClinVar VariationId is 364341.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.914 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ABCA1	NM_005502.4	MANE Select	c.*1896G>A		3_prime_UTR	Exon 50 of 50	NP_005493.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ABCA1	ENST00000374736.8	TSL:1 MANE Select	c.*1896G>A		3_prime_UTR	Exon 50 of 50	ENSP00000363868.3	O95477
	ABCA1	ENST00000678995.1		c.*1896G>A		3_prime_UTR	Exon 50 of 50	ENSP00000504612.1	A0A7I2V5U0

Frequencies

GnomAD3 genomes AF: 0.850 AC: 129105 AN: 151928 Hom.: 55177 Cov.: 32

Gnomad AFR AF: 0.922

Gnomad AMI AF: 0.822

Gnomad AMR AF: 0.902

Gnomad ASJ AF: 0.833

Gnomad EAS AF: 0.818

Gnomad SAS AF: 0.821

Gnomad FIN AF: 0.707

Gnomad MID AF: 0.841

Gnomad NFE AF: 0.822

Gnomad OTH AF: 0.856

GnomAD4 exome Data not reliable, filtered out with message: AC0 AC: 0 AN: 0 Hom.: 0 Cov.: 0 AC XY: 0 AN XY: 0

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AC: 0 AN: 0

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AC: 0 AN: 0

Other (OTH) AC: 0 AN: 0

GnomAD4 genome AF: 0.850 AC: 129223 AN: 152046 Hom.: 55237 Cov.: 32 AF XY: 0.845 AC XY: 62801 AN XY: 74288

African (AFR) AF: 0.922 AC: 38294 AN: 41532

American (AMR) AF: 0.902 AC: 13788 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.833 AC: 2888 AN: 3468

East Asian (EAS) AF: 0.817 AC: 4229 AN: 5174

South Asian (SAS) AF: 0.821 AC: 3960 AN: 4822

European-Finnish (FIN) AF: 0.707 AC: 7440 AN: 10518

Middle Eastern (MID) AF: 0.836 AC: 244 AN: 292

European-Non Finnish (NFE) AF: 0.822 AC: 55825 AN: 67932

Other (OTH) AF: 0.855 AC: 1805 AN: 2110

Alfa AF: 0.838 Hom.: 159102

Bravo AF: 0.867

Asia WGS AF: 0.837 AC: 2880 AN: 3440

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)
-	-	1	Hypoalphalipoproteinemia, primary, 1 (1)
-	-	1	Tangier disease (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	7.0
DANN	Benign	0.55
PhyloP100		0.052
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: rs363717; hg19: chr9-107544700;