chr22-43923801-G-A

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The ENST00000406117.6(PNPLA3):​c.-111G>A variant causes a 5 prime UTR, NMD transcript change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00208 in 1,087,008 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 Likely benign (★★).

Frequency

Genomes: 𝑓 0.0090 ( 30 hom., cov: 32)
Exomes 𝑓: 0.00096 ( 19 hom. )

Consequence

PNPLA3
ENST00000406117.6 5_prime_UTR, NMD_transcript

Scores

2

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.730
Variant links:
Genes affected
PNPLA3 (HGNC:18590): (patatin like phospholipase domain containing 3) The protein encoded by this gene is a triacylglycerol lipase that mediates triacylglycerol hydrolysis in adipocytes. The encoded protein, which appears to be membrane bound, may be involved in the balance of energy usage/storage in adipocytes. [provided by RefSeq, Jul 2008]

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.8).
BP6
Variant 22-43923801-G-A is Benign according to our data. Variant chr22-43923801-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 341923.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BS1
Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00897 (1365/152244) while in subpopulation AFR AF= 0.0312 (1296/41542). AF 95% confidence interval is 0.0298. There are 30 homozygotes in gnomad4. There are 649 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
BS2
High Homozygotes in GnomAd4 at 30 AR gene

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
PNPLA3NM_025225.3 linkuse as main transcript upstream_gene_variant ENST00000216180.8

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
PNPLA3ENST00000406117.6 linkuse as main transcriptc.-111G>A 5_prime_UTR_variant, NMD_transcript_variant 1/102
PNPLA3ENST00000216180.8 linkuse as main transcript upstream_gene_variant 1 NM_025225.3 P1Q9NST1-1
PNPLA3ENST00000423180.2 linkuse as main transcript upstream_gene_variant 2 Q9NST1-2

Frequencies

GnomAD3 genomes
AF:
0.00892
AC:
1357
AN:
152130
Hom.:
30
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.0311
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00262
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00316
Gnomad NFE
AF:
0.000250
Gnomad OTH
AF:
0.00478
GnomAD4 exome
AF:
0.000962
AC:
899
AN:
934764
Hom.:
19
Cov.:
12
AF XY:
0.000925
AC XY:
427
AN XY:
461756
show subpopulations
Gnomad4 AFR exome
AF:
0.0359
Gnomad4 AMR exome
AF:
0.00191
Gnomad4 ASJ exome
AF:
0.0000639
Gnomad4 EAS exome
AF:
0.000152
Gnomad4 SAS exome
AF:
0.0000605
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.000141
Gnomad4 OTH exome
AF:
0.00256
GnomAD4 genome
AF:
0.00897
AC:
1365
AN:
152244
Hom.:
30
Cov.:
32
AF XY:
0.00872
AC XY:
649
AN XY:
74456
show subpopulations
Gnomad4 AFR
AF:
0.0312
Gnomad4 AMR
AF:
0.00261
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.000250
Gnomad4 OTH
AF:
0.00520
Alfa
AF:
0.00867
Hom.:
5
Bravo
AF:
0.0104
Asia WGS
AF:
0.00926
AC:
32
AN:
3470

ClinVar

Significance: Likely benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

NAFLD1 Benign:1
Likely benign, criteria provided, single submitterclinical testingIllumina Laboratory Services, IlluminaJan 13, 2018This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as likely benign is not then subjected to further curation. The score for this variant resulted in a classification of likely benign for this disease. -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.80
CADD
Benign
2.4
DANN
Benign
0.92
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.0

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.16
Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs548897706; hg19: chr22-44319681; API