11-116837537-C-T

Variant names:

• chr11-116837537-C-T
• rs1799837
• ENST00000375323.5:c.-150G>A

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BS1 BS2

The ENST00000375323.5(APOA1):​c.-150G>A variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00689 in 956,534 control chromosomes in the GnomAD database, including 49 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.0060 (11 hom., cov: 33)
  • Exomes 𝑓: 0.0071 (38 hom.)
• Consequence: APOA1 ENST00000375323.5 5_prime_UTR
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.285
• Publications: 119 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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.79).
• BP6: Variant 11-116837537-C-T is Benign according to our data. Variant chr11-116837537-C-T is described in ClinVar as Benign. ClinVar VariationId is 3780821.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population nfe. GnomAd4 allele frequency = 0.006 (913/152272) while in subpopulation NFE AF = 0.00782 (532/68004). AF 95% confidence interval is 0.00727. There are 11 homozygotes in GnomAd4. There are 417 alleles in the male GnomAd4 subpopulation. Median coverage is 33. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 11 AD,AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000375323.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	APOA1	NM_000039.3	MANE Select	c.-21+68G>A		intron	N/A	NP_000030.1
	APOA1	NM_001318017.2		c.-30G>A		5_prime_UTR	Exon 1 of 4	NP_001304946.1
	APOA1	NM_001425090.1		c.-39G>A		5_prime_UTR	Exon 1 of 4	NP_001412019.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	APOA1	ENST00000375323.5	TSL:1	c.-150G>A		5_prime_UTR	Exon 1 of 3	ENSP00000364472.1
	APOA1	ENST00000236850.5	TSL:1 MANE Select	c.-21+68G>A		intron	N/A	ENSP00000236850.3
	APOA1	ENST00000375320.5	TSL:3	c.-30G>A		5_prime_UTR	Exon 1 of 4	ENSP00000364469.1

Frequencies

GnomAD3 genomes AF: 0.00600 AC: 913 AN: 152156 Hom.: 11 Cov.: 33

Gnomad AFR AF: 0.00101

Gnomad AMI AF: 0.0877

Gnomad AMR AF: 0.00582

Gnomad ASJ AF: 0.0357

Gnomad EAS AF: 0.000193

Gnomad SAS AF: 0.00166

Gnomad FIN AF: 0.00151

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.00782

Gnomad OTH AF: 0.00957

GnomAD4 exome AF: 0.00706 AC: 5680 AN: 804262 Hom.: 38 Cov.: 11 AF XY: 0.00715 AC XY: 2938 AN XY: 410886

African (AFR) AF: 0.00104 AC: 21 AN: 20162

American (AMR) AF: 0.00633 AC: 192 AN: 30326

Ashkenazi Jewish (ASJ) AF: 0.0307 AC: 557 AN: 18166

East Asian (EAS) AF: 0.0000305 AC: 1 AN: 32838

South Asian (SAS) AF: 0.00161 AC: 97 AN: 60166

European-Finnish (FIN) AF: 0.00143 AC: 65 AN: 45312

Middle Eastern (MID) AF: 0.00441 AC: 19 AN: 4306

European-Non Finnish (NFE) AF: 0.00798 AC: 4428 AN: 554822

Other (OTH) AF: 0.00786 AC: 300 AN: 38164

GnomAD4 genome AF: 0.00600 AC: 913 AN: 152272 Hom.: 11 Cov.: 33 AF XY: 0.00560 AC XY: 417 AN XY: 74446

African (AFR) AF: 0.00101 AC: 42 AN: 41560

American (AMR) AF: 0.00582 AC: 89 AN: 15302

Ashkenazi Jewish (ASJ) AF: 0.0357 AC: 124 AN: 3472

East Asian (EAS) AF: 0.000193 AC: 1 AN: 5178

South Asian (SAS) AF: 0.00166 AC: 8 AN: 4816

European-Finnish (FIN) AF: 0.00151 AC: 16 AN: 10624

Middle Eastern (MID) AF: 0.00342 AC: 1 AN: 292

European-Non Finnish (NFE) AF: 0.00782 AC: 532 AN: 68004

Other (OTH) AF: 0.00947 AC: 20 AN: 2112

Alfa AF: 0.00683 Hom.: 1

Bravo AF: 0.00685

Asia WGS AF: 0.00231 AC: 8 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

Familial visceral amyloidosis, Ostertag type Benign:1

Jul 30, 2021

Department of Pathology and Laboratory Medicine, Sinai Health System

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: research

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
CADD	Benign	0.068
DANN	Benign	0.60
PhyloP100		-0.28
PromoterAI		0.019	Neutral
Mutation Taster		=100/0	polymorphism

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: rs1799837; hg19: chr11-116708253;