1-26427451-T-C

Position:

• chr1-26427451-T-C

Variant summary

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

The NM_024674.6(LIN28A):​c.*993T>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.438 in 152,562 control chromosomes in the GnomAD database, including 16,176 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 0.44 (16118 hom., cov: 32)
  • Exomes 𝑓: 0.51 (58 hom.)
• Consequence: LIN28A NM_024674.6 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.966

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=-0.71).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.532 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
LIN28A	NM_024674.6	c.*993T>C		3_prime_UTR_variant	4/4	ENST00000326279.11	NP_078950.1
LIN28A	XM_011542148.3	c.*216T>C		3_prime_UTR_variant	5/5		XP_011540450.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
LIN28A	ENST00000326279.11	c.*993T>C		3_prime_UTR_variant	4/4	1	NM_024674.6	ENSP00000363314.3
LIN28A	ENST00000254231.4	c.*993T>C		3_prime_UTR_variant	4/5	1		ENSP00000254231.4

Frequencies

GnomAD3 genomes AF: 0.438 AC: 66590 AN: 151998 Hom.: 16108 Cov.: 32

Gnomad AFR AF: 0.257

Gnomad AMI AF: 0.432

Gnomad AMR AF: 0.541

Gnomad ASJ AF: 0.564

Gnomad EAS AF: 0.139

Gnomad SAS AF: 0.346

Gnomad FIN AF: 0.515

Gnomad MID AF: 0.497

Gnomad NFE AF: 0.535

Gnomad OTH AF: 0.460

GnomAD4 exome AF: 0.507 AC: 225 AN: 444 Hom.: 58 Cov.: 0 AF XY: 0.507 AC XY: 137 AN XY: 270

Gnomad4 FIN exome AF: 0.507

Gnomad4 NFE exome AF: 0.571

Gnomad4 OTH exome AF: 0.333

GnomAD4 genome AF: 0.438 AC: 66638 AN: 152118 Hom.: 16118 Cov.: 32 AF XY: 0.437 AC XY: 32452 AN XY: 74344

Gnomad4 AFR AF: 0.257

Gnomad4 AMR AF: 0.541

Gnomad4 ASJ AF: 0.564

Gnomad4 EAS AF: 0.139

Gnomad4 SAS AF: 0.347

Gnomad4 FIN AF: 0.515

Gnomad4 NFE AF: 0.535

Gnomad4 OTH AF: 0.457

Alfa AF: 0.477 Hom.: 2341

Bravo AF: 0.437

Asia WGS AF: 0.246 AC: 858 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.71
CADD	Benign	3.9
DANN	Benign	0.81

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: rs3811463; hg19: chr1-26753942; COSMIC: COSV52576545; COSMIC: COSV52576545;