rs2070665

Variant names:

• chr11-116836968-A-G
• rs2070665
• NM_000039.3:c.200+33T>C

Your query was ambiguous. Multiple possible variants found:

• chr11-116836968-A-G
• chr11-116836968-A-C

Variant summary

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

The NM_000039.3(APOA1):​c.200+33T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.893 in 1,612,302 control chromosomes in the GnomAD database, including 647,000 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.88 (59864 hom., cov: 33)
  • Exomes 𝑓: 0.89 (587136 hom.)
• Consequence: APOA1 NM_000039.3 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:5
• Conservation: PhyloP100: -4.65
• Publications: 42 publications found

Genes affected

APOA1 (HGNC:600): (apolipoprotein A1) This gene encodes apolipoprotein A-I, which is the major protein component of high density lipoprotein (HDL) in plasma. The encoded preproprotein is proteolytically processed to generate the mature protein, which promotes cholesterol efflux from tissues to the liver for excretion, and is a cofactor for lecithin cholesterolacyltransferase (LCAT), an enzyme responsible for the formation of most plasma cholesteryl esters. This gene is closely linked with two other apolipoprotein genes on chromosome 11. Defects in this gene are associated with HDL deficiencies, including Tangier disease, and with systemic non-neuropathic amyloidosis. Alternative splicing results in multiple transcript variants, at least one of which encodes a preproprotein. [provided by RefSeq, Dec 2015]

APOA1-AS (HGNC:40079): (APOA1 antisense RNA)

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BP6: Variant 11-116836968-A-G is Benign according to our data. Variant chr11-116836968-A-G is described in ClinVar as Benign. ClinVar VariationId is 1251605.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.912 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000039.3. 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
	APOA1	NM_000039.3	MANE Select	c.200+33T>C		intron	N/A	NP_000030.1	A0A024R3E3
	APOA1	NM_001318017.2		c.200+33T>C		intron	N/A	NP_001304946.1	A0A024R3E3
	APOA1	NM_001318018.2		c.200+33T>C		intron	N/A	NP_001304947.1	P02647

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	APOA1	ENST00000236850.5	TSL:1 MANE Select	c.200+33T>C		intron	N/A	ENSP00000236850.3	P02647
	APOA1	ENST00000375323.5	TSL:1	c.200+33T>C		intron	N/A	ENSP00000364472.1	P02647
	APOA1	ENST00000855312.1		c.200+33T>C		intron	N/A	ENSP00000525371.1

Frequencies

GnomAD3 genomes AF: 0.884 AC: 134544 AN: 152148 Hom.: 59831 Cov.: 33

Gnomad AFR AF: 0.907

Gnomad AMI AF: 0.970

Gnomad AMR AF: 0.820

Gnomad ASJ AF: 0.859

Gnomad EAS AF: 0.668

Gnomad SAS AF: 0.684

Gnomad FIN AF: 0.873

Gnomad MID AF: 0.854

Gnomad NFE AF: 0.918

Gnomad OTH AF: 0.878

GnomAD2 exomes AF: 0.849 AC: 212034 AN: 249616 AF XY: 0.845

Gnomad AFR exome AF: 0.900

Gnomad AMR exome AF: 0.798

Gnomad ASJ exome AF: 0.861

Gnomad EAS exome AF: 0.689

Gnomad FIN exome AF: 0.879

Gnomad NFE exome AF: 0.918

Gnomad OTH exome AF: 0.870

GnomAD4 exome AF: 0.893 AC: 1304481 AN: 1460036 Hom.: 587136 Cov.: 37 AF XY: 0.887 AC XY: 644609 AN XY: 726430

African (AFR) AF: 0.904 AC: 30254 AN: 33450

American (AMR) AF: 0.801 AC: 35834 AN: 44714

Ashkenazi Jewish (ASJ) AF: 0.862 AC: 22528 AN: 26130

East Asian (EAS) AF: 0.625 AC: 24810 AN: 39688

South Asian (SAS) AF: 0.699 AC: 60255 AN: 86216

European-Finnish (FIN) AF: 0.880 AC: 46250 AN: 52576

Middle Eastern (MID) AF: 0.855 AC: 4922 AN: 5758

European-Non Finnish (NFE) AF: 0.924 AC: 1026523 AN: 1111146

Other (OTH) AF: 0.880 AC: 53105 AN: 60358

GnomAD4 genome AF: 0.884 AC: 134632 AN: 152266 Hom.: 59864 Cov.: 33 AF XY: 0.876 AC XY: 65199 AN XY: 74442

African (AFR) AF: 0.907 AC: 37675 AN: 41546

American (AMR) AF: 0.820 AC: 12534 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.859 AC: 2982 AN: 3472

East Asian (EAS) AF: 0.668 AC: 3449 AN: 5162

South Asian (SAS) AF: 0.684 AC: 3299 AN: 4824

European-Finnish (FIN) AF: 0.873 AC: 9266 AN: 10616

Middle Eastern (MID) AF: 0.854 AC: 251 AN: 294

European-Non Finnish (NFE) AF: 0.918 AC: 62446 AN: 68034

Other (OTH) AF: 0.874 AC: 1845 AN: 2112

Alfa AF: 0.906 Hom.: 105815

Bravo AF: 0.888

Asia WGS AF: 0.681 AC: 2374 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)
-	-	1	Familial visceral amyloidosis, Ostertag type (1)
-	-	1	Hypoalphalipoproteinemia, primary, 2 (1)
-	-	1	Hypoalphalipoproteinemia, primary, 2, intermediate (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.28
DANN	Benign	0.35
PhyloP100		-4.7
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
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: rs2070665; hg19: chr11-116707684;