rs12728900

chr1-26420316-G-Achr1-26420316-G-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_024674.6(LIN28A):c.229-4987G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.281 in 151,802 control chromosomes in the GnomAD database, including 6,720 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 0.28 (6720 hom., cov: 30)
• Consequence: LIN28A NM_024674.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.30

Genes affected

LIN28A (HGNC:15986): (lin-28 homolog A) This gene encodes a LIN-28 family RNA-binding protein that acts as a posttranscriptional regulator of genes involved in developmental timing and self-renewal in embryonic stem cells. The encoded protein functions through direct interaction with target mRNAs and by disrupting the maturation of certain miRNAs involved in embryonic development. This protein prevents the terminal processing of the LET7 family of microRNAs which are major regulators of cellular growth and differentiation. Aberrant expression of this gene is associated with cancer progression in multiple tissues. [provided by RefSeq, Sep 2015]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.414 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
LIN28A	NM_024674.6	c.229-4987G>A		intron_variant		ENST00000326279.11
LIN28A	XM_011542148.3	c.229-4987G>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
LIN28A	ENST00000326279.11	c.229-4987G>A		intron_variant		1	NM_024674.6	P1
LIN28A	ENST00000254231.4	c.229-4987G>A		intron_variant		1		P1

Frequencies

GnomAD3 genomes AF: 0.281 AC: 42625 AN: 151684 Hom.: 6709 Cov.: 30

Gnomad AFR AF: 0.419

Gnomad AMI AF: 0.153

Gnomad AMR AF: 0.211

Gnomad ASJ AF: 0.198

Gnomad EAS AF: 0.138

Gnomad SAS AF: 0.179

Gnomad FIN AF: 0.198

Gnomad MID AF: 0.342

Gnomad NFE AF: 0.250

Gnomad OTH AF: 0.277

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

GnomAD4 genome AF: 0.281 AC: 42682 AN: 151802 Hom.: 6720 Cov.: 30 AF XY: 0.275 AC XY: 20401 AN XY: 74170

Gnomad4 AFR AF: 0.419

Gnomad4 AMR AF: 0.211

Gnomad4 ASJ AF: 0.198

Gnomad4 EAS AF: 0.138

Gnomad4 SAS AF: 0.179

Gnomad4 FIN AF: 0.198

Gnomad4 NFE AF: 0.250

Gnomad4 OTH AF: 0.273

Alfa AF: 0.248 Hom.: 6632

Bravo AF: 0.288

Asia WGS AF: 0.153 AC: 533 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
Cadd	Benign	0.32
Dann	Benign	0.76

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

Publications

LitVar

Other links and lift over

dbSNP: rs12728900; hg19: chr1-26746807;