Genetic Variant NM_024674.6:c.*993T>C (chr1-26427451-T-C) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

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

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.966

Publications

27 publications found

Variant links:

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]

LIN28A links:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
LIN28A	NM_024674.6 link	c.*993T>C		3_prime_UTR_variant	Exon 4 of 4	ENST00000326279.11	NP_078950.1	Q9H9Z2
LIN28A	XM_011542148.3 link	c.*216T>C		3_prime_UTR_variant	Exon 5 of 5		XP_011540450.1	Q9H9Z2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
LIN28A	ENST00000326279.11 link	c.*993T>C		3_prime_UTR_variant	Exon 4 of 4	1	NM_024674.6	ENSP00000363314.3		Q9H9Z2
LIN28A	ENST00000254231.4 link	c.*993T>C		3_prime_UTR_variant	Exon 4 of 5	1		ENSP00000254231.4		Q9H9Z2

Frequencies

GnomAD3 genomes

AF:

0.438

AC:

66590

AN:

151998

Hom.:

16108

Cov.:

show subpopulations

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.:

Cov.:

AF XY:

0.507

AC XY:

137

AN XY:

270

show subpopulations

African (AFR)

AC:

AN:

American (AMR)

AC:

AN:

Ashkenazi Jewish (ASJ)

AC:

AN:

East Asian (EAS)

AC:

AN:

South Asian (SAS)

AC:

AN:

European-Finnish (FIN)

AF:

0.507

AC:

215

AN:

424

Middle Eastern (MID)

AC:

AN:

European-Non Finnish (NFE)

AF:

0.571

AC:

AN:

Other (OTH)

AF:

0.333

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.509

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.438

AC:

66638

AN:

152118

Hom.:

16118

Cov.:

AF XY:

0.437

AC XY:

32452

AN XY:

74344

show subpopulations

African (AFR)

AF:

0.257

AC:

10685

AN:

41508

American (AMR)

AF:

0.541

AC:

8271

AN:

15276

Ashkenazi Jewish (ASJ)

AF:

0.564

AC:

1957

AN:

3470

East Asian (EAS)

AF:

0.139

AC:

719

AN:

5176

South Asian (SAS)

AF:

0.347

AC:

1676

AN:

4826

European-Finnish (FIN)

AF:

0.515

AC:

5441

AN:

10570

Middle Eastern (MID)

AF:

0.493

AC:

145

AN:

294

European-Non Finnish (NFE)

AF:

0.535

AC:

36382

AN:

67970

Other (OTH)

AF:

0.457

AC:

968

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.505

Heterozygous variant carriers

1828

3656

5485

7313

9141

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.393

Hom.:

2858

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

(source)

DANN

Benign

0.81

PhyloP100

0.97

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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NM_024674.6:c.*993T>C

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over