rs5070

Variant names:

• chr11-116837304-A-G
• rs5070
• NM_000039.3:c.43+41T>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.43+41T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.638 in 1,583,486 control chromosomes in the GnomAD database, including 332,812 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.59 (27300 hom., cov: 32)
  • Exomes 𝑓: 0.64 (305512 hom.)
• Consequence: APOA1 NM_000039.3 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:5
• Conservation: PhyloP100: 1.67
• Publications: 32 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=-0.84).
• BP6: Variant 11-116837304-A-G is Benign according to our data. Variant chr11-116837304-A-G is described in ClinVar as Benign. ClinVar VariationId is 1225953.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.678 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
APOA1	NM_000039.3	c.43+41T>C		intron_variant	Intron 2 of 3	ENST00000236850.5	NP_000030.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
APOA1	ENST00000236850.5	c.43+41T>C		intron_variant	Intron 2 of 3	1	NM_000039.3	ENSP00000236850.3

Frequencies

GnomAD3 genomes AF: 0.590 AC: 89601 AN: 151904 Hom.: 27297 Cov.: 32

Gnomad AFR AF: 0.522

Gnomad AMI AF: 0.822

Gnomad AMR AF: 0.536

Gnomad ASJ AF: 0.615

Gnomad EAS AF: 0.269

Gnomad SAS AF: 0.369

Gnomad FIN AF: 0.565

Gnomad MID AF: 0.500

Gnomad NFE AF: 0.683

Gnomad OTH AF: 0.583

GnomAD2 exomes AF: 0.557 AC: 112149 AN: 201366 AF XY: 0.557

Gnomad AFR exome AF: 0.514

Gnomad AMR exome AF: 0.458

Gnomad ASJ exome AF: 0.624

Gnomad EAS exome AF: 0.268

Gnomad FIN exome AF: 0.571

Gnomad NFE exome AF: 0.686

Gnomad OTH exome AF: 0.599

GnomAD4 exome AF: 0.643 AC: 920676 AN: 1431466 Hom.: 305512 Cov.: 34 AF XY: 0.636 AC XY: 450989 AN XY: 709512

African (AFR) AF: 0.511 AC: 16874 AN: 33052

American (AMR) AF: 0.468 AC: 18189 AN: 38844

Ashkenazi Jewish (ASJ) AF: 0.619 AC: 15800 AN: 25522

East Asian (EAS) AF: 0.236 AC: 9137 AN: 38698

South Asian (SAS) AF: 0.386 AC: 32138 AN: 83358

European-Finnish (FIN) AF: 0.573 AC: 29327 AN: 51222

Middle Eastern (MID) AF: 0.530 AC: 3034 AN: 5720

European-Non Finnish (NFE) AF: 0.694 AC: 760017 AN: 1095718

Other (OTH) AF: 0.609 AC: 36160 AN: 59332

GnomAD4 genome AF: 0.590 AC: 89624 AN: 152020 Hom.: 27300 Cov.: 32 AF XY: 0.579 AC XY: 43037 AN XY: 74320

African (AFR) AF: 0.522 AC: 21641 AN: 41464

American (AMR) AF: 0.535 AC: 8179 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.615 AC: 2133 AN: 3466

East Asian (EAS) AF: 0.269 AC: 1389 AN: 5162

South Asian (SAS) AF: 0.369 AC: 1777 AN: 4812

European-Finnish (FIN) AF: 0.565 AC: 5971 AN: 10568

Middle Eastern (MID) AF: 0.514 AC: 151 AN: 294

European-Non Finnish (NFE) AF: 0.683 AC: 46420 AN: 67946

Other (OTH) AF: 0.576 AC: 1217 AN: 2112

Alfa AF: 0.619 Hom.: 5934

Bravo AF: 0.587

Asia WGS AF: 0.302 AC: 1052 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Aug 30, 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

- -

Hypoalphalipoproteinemia, primary, 2, intermediate Benign:1

Dec 05, 2021

Genome-Nilou Lab

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Hypoalphalipoproteinemia, primary, 2 Benign:1

Dec 05, 2021

Genome-Nilou Lab

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Familial visceral amyloidosis, Ostertag type Benign:1

Dec 05, 2021

Genome-Nilou Lab

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	11
DANN	Benign	0.57
PhyloP100		1.7
PromoterAI		0.017	Neutral
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: rs5070; hg19: chr11-116708020; COSMIC: COSV52636279; COSMIC: COSV52636279;