rs3811464

Variant names:

• chr1-26410652-G-A
• rs3811464
• NM_024674.6:c.-240G>A

Variant summary

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

The NM_024674.6(LIN28A):​c.-240G>A variant causes a upstream gene change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.47 in 551,102 control chromosomes in the GnomAD database, including 64,936 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 0.42 (14210 hom., cov: 19)
  • Exomes 𝑓: 0.49 (50726 hom.)
• Consequence: LIN28A NM_024674.6 upstream_gene
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.51

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=-0.76).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.53 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LIN28A	NM_024674.6	c.-240G>A		upstream_gene_variant		ENST00000326279.11	NP_078950.1
LIN28A	XM_011542148.3	c.-240G>A		upstream_gene_variant			XP_011540450.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
LIN28A	ENST00000326279.11	c.-240G>A		upstream_gene_variant		1	NM_024674.6	ENSP00000363314.3
LIN28A	ENST00000254231.4	c.-240G>A		upstream_gene_variant		1		ENSP00000254231.4

Frequencies

GnomAD3 genomes AF: 0.423 AC: 60119 AN: 142096 Hom.: 14202 Cov.: 19

Gnomad AFR AF: 0.218

Gnomad AMI AF: 0.397

Gnomad AMR AF: 0.460

Gnomad ASJ AF: 0.497

Gnomad EAS AF: 0.147

Gnomad SAS AF: 0.470

Gnomad FIN AF: 0.509

Gnomad MID AF: 0.412

Gnomad NFE AF: 0.535

Gnomad OTH AF: 0.415

GnomAD4 exome AF: 0.486 AC: 198662 AN: 408876 Hom.: 50726 AF XY: 0.487 AC XY: 105248 AN XY: 216154

Gnomad4 AFR exome AF: 0.218

Gnomad4 AMR exome AF: 0.453

Gnomad4 ASJ exome AF: 0.485

Gnomad4 EAS exome AF: 0.184

Gnomad4 SAS exome AF: 0.470

Gnomad4 FIN exome AF: 0.491

Gnomad4 NFE exome AF: 0.534

Gnomad4 OTH exome AF: 0.458

GnomAD4 genome AF: 0.423 AC: 60148 AN: 142226 Hom.: 14210 Cov.: 19 AF XY: 0.421 AC XY: 28987 AN XY: 68848

Gnomad4 AFR AF: 0.218

Gnomad4 AMR AF: 0.460

Gnomad4 ASJ AF: 0.497

Gnomad4 EAS AF: 0.146

Gnomad4 SAS AF: 0.471

Gnomad4 FIN AF: 0.509

Gnomad4 NFE AF: 0.535

Gnomad4 OTH AF: 0.412

Alfa AF: 0.475 Hom.: 2678

Bravo AF: 0.403

Asia WGS AF: 0.278 AC: 965 AN: 3468

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.76
CADD	Benign	14
DANN	Benign	0.85

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs3811464; hg19: chr1-26737143;