rs24168

Variant names:

• chr7-130876526-A-G
• rs24168
• ENST00000447430.1:n.156+14324A>G

Variant summary

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

The ENST00000447430.1(LINC00513):​n.156+14324A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.494 in 152,130 control chromosomes in the GnomAD database, including 19,924 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 0.49 (19924 hom., cov: 33)
• Consequence: LINC00513 ENST00000447430.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.143
• Publications: 10 publications found

Genes affected

LINC00513 (HGNC:43566): (long intergenic non-protein coding RNA 513)

LINC-PINT (HGNC:26885): (long intergenic non-protein coding RNA, p53 induced transcript) Predicted to act upstream of or within several processes, including adipose tissue development; adult somatic muscle development; and hair follicle development. [provided by Alliance of Genome Resources, Apr 2022]

MIR29A (HGNC:31616): (microRNA 29a) microRNAs (miRNAs) are short (20-24 nt) non-coding RNAs that are involved in post-transcriptional regulation of gene expression in multicellular organisms by affecting both the stability and translation of mRNAs. miRNAs are transcribed by RNA polymerase II as part of capped and polyadenylated primary transcripts (pri-miRNAs) that can be either protein-coding or non-coding. The primary transcript is cleaved by the Drosha ribonuclease III enzyme to produce an approximately 70-nt stem-loop precursor miRNA (pre-miRNA), which is further cleaved by the cytoplasmic Dicer ribonuclease to generate the mature miRNA and antisense miRNA star (miRNA*) products. The mature miRNA is incorporated into a RNA-induced silencing complex (RISC), which recognizes target mRNAs through imperfect base pairing with the miRNA and most commonly results in translational inhibition or destabilization of the target mRNA. The RefSeq represents the predicted microRNA stem-loop. [provided by RefSeq, Sep 2009]

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.593 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MIR29A	NR_029503.1	n.*221T>C		downstream_gene_variant
MIR29A	unassigned_transcript_1312	n.*222T>C		downstream_gene_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
LINC00513	ENST00000447430.1	n.156+14324A>G		intron_variant	Intron 2 of 4	5
LINC-PINT	ENST00000642963.1	n.593+7791T>C		intron_variant	Intron 5 of 6
LINC-PINT	ENST00000643866.1	n.1698-3887T>C		intron_variant	Intron 4 of 6

Frequencies

GnomAD3 genomes AF: 0.494 AC: 75075 AN: 152012 Hom.: 19927 Cov.: 33

Gnomad AFR AF: 0.294

Gnomad AMI AF: 0.491

Gnomad AMR AF: 0.451

Gnomad ASJ AF: 0.537

Gnomad EAS AF: 0.611

Gnomad SAS AF: 0.591

Gnomad FIN AF: 0.656

Gnomad MID AF: 0.560

Gnomad NFE AF: 0.582

Gnomad OTH AF: 0.500

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

GnomAD4 genome AF: 0.494 AC: 75091 AN: 152130 Hom.: 19924 Cov.: 33 AF XY: 0.498 AC XY: 37067 AN XY: 74384

African (AFR) AF: 0.294 AC: 12181 AN: 41492

American (AMR) AF: 0.451 AC: 6889 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.537 AC: 1862 AN: 3468

East Asian (EAS) AF: 0.611 AC: 3158 AN: 5170

South Asian (SAS) AF: 0.589 AC: 2833 AN: 4810

European-Finnish (FIN) AF: 0.656 AC: 6951 AN: 10592

Middle Eastern (MID) AF: 0.551 AC: 162 AN: 294

European-Non Finnish (NFE) AF: 0.582 AC: 39549 AN: 67996

Other (OTH) AF: 0.501 AC: 1059 AN: 2112

Alfa AF: 0.540 Hom.: 2909

Bravo AF: 0.469

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	7.0
DANN	Benign	0.45
PhyloP100		0.14

Splicing

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

Other links and lift over

dbSNP: rs24168; hg19: chr7-130561285; COSMIC: COSV62996923;