rs40457

Variant names:

• chr8-89811459-A-G
• rs40457
• ENST00000814457.1:n.650-85818T>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000814457.1(PARAIL):​n.650-85818T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.574 in 152,024 control chromosomes in the GnomAD database, including 26,242 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain risk allele (no stars).

• Frequency: Genomes: 𝑓 0.57 (26242 hom., cov: 31)
• Consequence: PARAIL ENST00000814457.1 intron
• Clinical Significance: Uncertain risk allele no assertion criteria provided O:1
• Conservation: PhyloP100: 1.97
• Publications: 25 publications found

Genes affected

PARAIL (HGNC:55545): (palmitic acid regulated anti-inflammatory lncRNA)

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.734 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PARAIL	ENST00000814457.1	n.650-85818T>C		intron_variant	Intron 2 of 3
PARAIL	ENST00000814510.1	n.246-47422T>C		intron_variant	Intron 2 of 2
PARAIL	ENST00000814511.1	n.518-47422T>C		intron_variant	Intron 2 of 2
PARAIL	ENST00000814512.1	n.258-47422T>C		intron_variant	Intron 2 of 2

Frequencies

GnomAD3 genomes AF: 0.573 AC: 87110 AN: 151904 Hom.: 26214 Cov.: 31

Gnomad AFR AF: 0.740

Gnomad AMI AF: 0.432

Gnomad AMR AF: 0.485

Gnomad ASJ AF: 0.391

Gnomad EAS AF: 0.286

Gnomad SAS AF: 0.348

Gnomad FIN AF: 0.622

Gnomad MID AF: 0.623

Gnomad NFE AF: 0.533

Gnomad OTH AF: 0.560

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.574 AC: 87195 AN: 152024 Hom.: 26242 Cov.: 31 AF XY: 0.569 AC XY: 42287 AN XY: 74286

African (AFR) AF: 0.740 AC: 30714 AN: 41480

American (AMR) AF: 0.485 AC: 7406 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.391 AC: 1358 AN: 3470

East Asian (EAS) AF: 0.286 AC: 1476 AN: 5164

South Asian (SAS) AF: 0.347 AC: 1676 AN: 4826

European-Finnish (FIN) AF: 0.622 AC: 6566 AN: 10556

Middle Eastern (MID) AF: 0.619 AC: 182 AN: 294

European-Non Finnish (NFE) AF: 0.534 AC: 36250 AN: 67942

Other (OTH) AF: 0.558 AC: 1173 AN: 2104

Alfa AF: 0.533 Hom.: 102727

Bravo AF: 0.575

Asia WGS AF: 0.353 AC: 1227 AN: 3478

ClinVar

Significance: Uncertain risk allele

Submissions summary: Other:1

Revision: no assertion criteria provided

Submissions by phenotype

Leprosy, susceptibility to, 1 Other:1

Jun 10, 2022

Centro Dermatológico Federico Lleras Acosta, Hospital Universitario Centro Dermatológico Federico Lleras Acosta

Significance: Uncertain risk allele

Review Status: no assertion criteria provided

Collection Method: case-control

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	11
DANN	Benign	0.86
PhyloP100		2.0

Splicing

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

Other links and lift over

dbSNP: rs40457; hg19: chr8-90823687;