14-88087524-A-G

Variant names:

• chr14-88087524-A-G
• rs4899940
• ENST00000668342.3:n.1113A>G

Variant summary

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

The ENST00000668342.3(HISLA):​n.1113A>G variant causes a non coding transcript exon change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.555 in 151,730 control chromosomes in the GnomAD database, including 23,779 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.56 (23779 hom., cov: 31)
• Consequence: HISLA ENST00000668342.3 non_coding_transcript_exon
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.283
• Publications: 12 publications found

Genes affected

HISLA (HGNC:49467): (HIF1A stabilizing long noncoding RNA)

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.6 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
HISLA	NR_046094.1	n.*178A>G		downstream_gene_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
HISLA	ENST00000668342.3	n.1113A>G		non_coding_transcript_exon_variant	Exon 3 of 3
HISLA	ENST00000553496.1	n.387-5603A>G		intron_variant	Intron 2 of 2	3
HISLA	ENST00000553929.5	n.328+3369A>G		intron_variant	Intron 3 of 3	3

Frequencies

GnomAD3 genomes AF: 0.555 AC: 84172 AN: 151612 Hom.: 23775 Cov.: 31

Gnomad AFR AF: 0.461

Gnomad AMI AF: 0.608

Gnomad AMR AF: 0.523

Gnomad ASJ AF: 0.602

Gnomad EAS AF: 0.571

Gnomad SAS AF: 0.564

Gnomad FIN AF: 0.615

Gnomad MID AF: 0.611

Gnomad NFE AF: 0.605

Gnomad OTH AF: 0.551

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

GnomAD4 genome AF: 0.555 AC: 84211 AN: 151730 Hom.: 23779 Cov.: 31 AF XY: 0.556 AC XY: 41259 AN XY: 74174

African (AFR) AF: 0.461 AC: 19083 AN: 41384

American (AMR) AF: 0.523 AC: 7944 AN: 15194

Ashkenazi Jewish (ASJ) AF: 0.602 AC: 2090 AN: 3470

East Asian (EAS) AF: 0.571 AC: 2935 AN: 5142

South Asian (SAS) AF: 0.565 AC: 2720 AN: 4818

European-Finnish (FIN) AF: 0.615 AC: 6497 AN: 10564

Middle Eastern (MID) AF: 0.605 AC: 178 AN: 294

European-Non Finnish (NFE) AF: 0.605 AC: 41058 AN: 67842

Other (OTH) AF: 0.546 AC: 1153 AN: 2112

Alfa AF: 0.571 Hom.: 13151

Bravo AF: 0.545

Asia WGS AF: 0.492 AC: 1715 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	4.2
DANN	Benign	0.73
PhyloP100		0.28

Splicing

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

Other links and lift over

dbSNP: rs4899940; hg19: chr14-88553868;