rs1800977

Variant names:

• chr9-104928169-G-A
• rs1800977
• ENST00000435915.1:n.358+259G>A

Your query was ambiguous. Multiple possible variants found:

• chr9-104928169-G-A
• chr9-104928169-G-C
• chr9-104928169-G-T

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The ENST00000435915.1(ENSG00000226334):​n.358+259G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.342 in 152,030 control chromosomes in the GnomAD database, including 9,340 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.34 (9332 hom., cov: 32)
  • Exomes 𝑓: 0.48 (8 hom.)
• Consequence: ENSG00000226334 ENST00000435915.1 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:4
• Conservation: PhyloP100: -0.0130
• Publications: 95 publications found

Genes affected

ENSG00000226334 (HGNC:):

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]

ABCA1 Gene-Disease associations (from GenCC):

• hypoalphalipoproteinemia, primary, 1

  Inheritance: AD Classification: DEFINITIVE, LIMITED Submitted by: Ambry Genetics, Labcorp Genetics (formerly Invitae)
• Tangier disease

  Inheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Orphanet, Labcorp Genetics (formerly Invitae), G2P
• apolipoprotein A-I deficiency

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.5).
• BP6: Variant 9-104928169-G-A is Benign according to our data. Variant chr9-104928169-G-A is described in ClinVar as Benign. ClinVar VariationId is 364481.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.434 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000435915.1. 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
	LOC105376196	NR_188620.1		n.1122+259G>A		intron	N/A
	ABCA1	NM_005502.4	MANE Select	c.-327C>T		upstream_gene	N/A	NP_005493.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ENSG00000226334	ENST00000435915.1	TSL:3	n.358+259G>A		intron	N/A
	ENSG00000226334	ENST00000820514.1		n.1164+259G>A		intron	N/A
	ABCA1	ENST00000374736.8	TSL:1 MANE Select	c.-327C>T		upstream_gene	N/A	ENSP00000363868.3	O95477

Frequencies

GnomAD3 genomes AF: 0.342 AC: 52004 AN: 151846 Hom.: 9328 Cov.: 32

Gnomad AFR AF: 0.255

Gnomad AMI AF: 0.558

Gnomad AMR AF: 0.442

Gnomad ASJ AF: 0.435

Gnomad EAS AF: 0.307

Gnomad SAS AF: 0.442

Gnomad FIN AF: 0.432

Gnomad MID AF: 0.364

Gnomad NFE AF: 0.347

Gnomad OTH AF: 0.351

GnomAD4 exome AF: 0.485 AC: 32 AN: 66 Hom.: 8 Cov.: 0 AF XY: 0.560 AC XY: 28 AN XY: 50

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AF: 1.00 AC: 2 AN: 2

East Asian (EAS) AF: 1.00 AC: 2 AN: 2

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AF: 1.00 AC: 2 AN: 2

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.444 AC: 24 AN: 54

Other (OTH) AF: 0.333 AC: 2 AN: 6

GnomAD4 genome AF: 0.342 AC: 52035 AN: 151964 Hom.: 9332 Cov.: 32 AF XY: 0.347 AC XY: 25793 AN XY: 74272

African (AFR) AF: 0.255 AC: 10558 AN: 41464

American (AMR) AF: 0.443 AC: 6771 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.435 AC: 1509 AN: 3472

East Asian (EAS) AF: 0.307 AC: 1572 AN: 5124

South Asian (SAS) AF: 0.441 AC: 2115 AN: 4798

European-Finnish (FIN) AF: 0.432 AC: 4555 AN: 10554

Middle Eastern (MID) AF: 0.371 AC: 109 AN: 294

European-Non Finnish (NFE) AF: 0.347 AC: 23610 AN: 67960

Other (OTH) AF: 0.346 AC: 729 AN: 2108

Alfa AF: 0.348 Hom.: 30239

Bravo AF: 0.340

Asia WGS AF: 0.355 AC: 1229 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)
-	-	1	Familial High Density Lipoprotein Deficiency (1)
-	-	1	Tangier disease (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.50
CADD	Benign	17
DANN	Benign	0.74
PhyloP100		-0.013
PromoterAI		0.077	Neutral
Mutation Taster		=300/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs1800977; hg19: chr9-107690450; COSMIC: COSV66059276; COSMIC: COSV66059276;