NM_000039.3:c.200+134T>C

Variant names:

• chr11-116836867-A-G
• rs5072
• NM_000039.3:c.200+134T>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+134T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.88 in 1,048,052 control chromosomes in the GnomAD database, including 409,572 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.88 (59814 hom., cov: 32)
  • Exomes 𝑓: 0.88 (349758 hom.)
• Consequence: APOA1 NM_000039.3 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -1.42
• Publications: 34 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=-0.87).
• BP6: Variant 11-116836867-A-G is Benign according to our data. Variant chr11-116836867-A-G is described in ClinVar as Benign. ClinVar VariationId is 1220811.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.911 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+134T>C		intron	N/A	NP_000030.1
	APOA1	NM_001318017.2		c.200+134T>C		intron	N/A	NP_001304946.1
	APOA1	NM_001318018.2		c.200+134T>C		intron	N/A	NP_001304947.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	APOA1	ENST00000236850.5	TSL:1 MANE Select	c.200+134T>C		intron	N/A	ENSP00000236850.3
	APOA1	ENST00000375323.5	TSL:1	c.200+134T>C		intron	N/A	ENSP00000364472.1
	APOA1	ENST00000855312.1		c.200+134T>C		intron	N/A	ENSP00000525371.1

Frequencies

GnomAD3 genomes AF: 0.884 AC: 134450 AN: 152062 Hom.: 59777 Cov.: 32

Gnomad AFR AF: 0.907

Gnomad AMI AF: 0.970

Gnomad AMR AF: 0.821

Gnomad ASJ AF: 0.859

Gnomad EAS AF: 0.667

Gnomad SAS AF: 0.683

Gnomad FIN AF: 0.873

Gnomad MID AF: 0.854

Gnomad NFE AF: 0.917

Gnomad OTH AF: 0.878

GnomAD4 exome AF: 0.879 AC: 787669 AN: 895872 Hom.: 349758 AF XY: 0.872 AC XY: 402709 AN XY: 461568

African (AFR) AF: 0.901 AC: 20438 AN: 22684

American (AMR) AF: 0.801 AC: 29950 AN: 37414

Ashkenazi Jewish (ASJ) AF: 0.860 AC: 17507 AN: 20350

East Asian (EAS) AF: 0.621 AC: 22583 AN: 36386

South Asian (SAS) AF: 0.697 AC: 47870 AN: 68678

European-Finnish (FIN) AF: 0.879 AC: 31560 AN: 35894

Middle Eastern (MID) AF: 0.851 AC: 2671 AN: 3138

European-Non Finnish (NFE) AF: 0.919 AC: 578328 AN: 629340

Other (OTH) AF: 0.876 AC: 36762 AN: 41988

GnomAD4 genome AF: 0.884 AC: 134544 AN: 152180 Hom.: 59814 Cov.: 32 AF XY: 0.876 AC XY: 65152 AN XY: 74382

African (AFR) AF: 0.907 AC: 37671 AN: 41526

American (AMR) AF: 0.820 AC: 12544 AN: 15298

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

East Asian (EAS) AF: 0.667 AC: 3446 AN: 5164

South Asian (SAS) AF: 0.683 AC: 3291 AN: 4816

European-Finnish (FIN) AF: 0.873 AC: 9241 AN: 10584

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

European-Non Finnish (NFE) AF: 0.917 AC: 62386 AN: 68000

Other (OTH) AF: 0.874 AC: 1847 AN: 2114

Alfa AF: 0.903 Hom.: 88682

Bravo AF: 0.888

Asia WGS AF: 0.682 AC: 2377 AN: 3478

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	0.28
DANN	Benign	0.67
PhyloP100		-1.4
Mutation Taster		=100/0	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: rs5072; hg19: chr11-116707583;