1-26426501-T-C

Variant names:

• chr1-26426501-T-C
• rs4659441
• NM_024674.6:c.*43T>C

Variant summary

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

The NM_024674.6(LIN28A):​c.*43T>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 0.808 in 1,546,482 control chromosomes in the GnomAD database, including 505,506 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 0.82 (51226 hom., cov: 32)
  • Exomes 𝑓: 0.81 (454280 hom.)
• Consequence: LIN28A NM_024674.6 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.34
• Publications: 18 publications found

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

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.86 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LIN28A	NM_024674.6	c.*43T>C		3_prime_UTR_variant	Exon 4 of 4	ENST00000326279.11	NP_078950.1
LIN28A	XM_011542148.3	c.*10+33T>C		intron_variant	Intron 4 of 4		XP_011540450.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
LIN28A	ENST00000326279.11	c.*43T>C		3_prime_UTR_variant	Exon 4 of 4	1	NM_024674.6	ENSP00000363314.3
LIN28A	ENST00000254231.4	c.*43T>C		3_prime_UTR_variant	Exon 4 of 5	1		ENSP00000254231.4

Frequencies

GnomAD3 genomes AF: 0.819 AC: 124621 AN: 152122 Hom.: 51181 Cov.: 32

Gnomad AFR AF: 0.847

Gnomad AMI AF: 0.724

Gnomad AMR AF: 0.872

Gnomad ASJ AF: 0.833

Gnomad EAS AF: 0.879

Gnomad SAS AF: 0.849

Gnomad FIN AF: 0.808

Gnomad MID AF: 0.826

Gnomad NFE AF: 0.786

Gnomad OTH AF: 0.813

GnomAD2 exomes AF: 0.831 AC: 196379 AN: 236428 AF XY: 0.828

Gnomad AFR exome AF: 0.850

Gnomad AMR exome AF: 0.911

Gnomad ASJ exome AF: 0.822

Gnomad EAS exome AF: 0.878

Gnomad FIN exome AF: 0.810

Gnomad NFE exome AF: 0.794

Gnomad OTH exome AF: 0.825

GnomAD4 exome AF: 0.807 AC: 1124661 AN: 1394242 Hom.: 454280 Cov.: 21 AF XY: 0.808 AC XY: 562425 AN XY: 696490

African (AFR) AF: 0.851 AC: 27262 AN: 32052

American (AMR) AF: 0.905 AC: 39082 AN: 43200

Ashkenazi Jewish (ASJ) AF: 0.824 AC: 21086 AN: 25584

East Asian (EAS) AF: 0.911 AC: 35715 AN: 39188

South Asian (SAS) AF: 0.851 AC: 71695 AN: 84250

European-Finnish (FIN) AF: 0.805 AC: 42669 AN: 52974

Middle Eastern (MID) AF: 0.830 AC: 4679 AN: 5640

European-Non Finnish (NFE) AF: 0.793 AC: 835210 AN: 1053180

Other (OTH) AF: 0.812 AC: 47263 AN: 58174

GnomAD4 genome AF: 0.819 AC: 124726 AN: 152240 Hom.: 51226 Cov.: 32 AF XY: 0.822 AC XY: 61205 AN XY: 74444

African (AFR) AF: 0.847 AC: 35177 AN: 41530

American (AMR) AF: 0.872 AC: 13347 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.833 AC: 2890 AN: 3470

East Asian (EAS) AF: 0.879 AC: 4556 AN: 5182

South Asian (SAS) AF: 0.849 AC: 4103 AN: 4832

European-Finnish (FIN) AF: 0.808 AC: 8568 AN: 10600

Middle Eastern (MID) AF: 0.820 AC: 241 AN: 294

European-Non Finnish (NFE) AF: 0.786 AC: 53464 AN: 68008

Other (OTH) AF: 0.814 AC: 1720 AN: 2112

Alfa AF: 0.803 Hom.: 9976

Bravo AF: 0.828

Asia WGS AF: 0.851 AC: 2959 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	0.15
DANN	Benign	0.54
PhyloP100		-2.3
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs4659441; hg19: chr1-26752992;