dbSNP rs3811464: LIN28A:c.-240G>A (chr1-26410652-G-A) – 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.-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

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.51

Publications

11 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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new If you want to explore the variant's impact on the transcript NM_024674.6, check out the Mutation Effect Viewer. This is especially useful for frameshift variants or if you want to visualize the effect of exon loss / intron retention.

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=-0.76).

BA1

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

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_024674.6. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LIN28A	NM_024674.6	MANE Select	c.-240G>A		upstream_gene	N/A	NP_078950.1	Q9H9Z2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LIN28A	ENST00000326279.11	TSL:1 MANE Select	c.-240G>A		upstream_gene	N/A	ENSP00000363314.3	Q9H9Z2
	LIN28A	ENST00000254231.4	TSL:1	c.-240G>A		upstream_gene	N/A	ENSP00000254231.4	Q9H9Z2

Frequencies

GnomAD3 genomes

AF:

0.423

AC:

60119

AN:

142096

Hom.:

14202

Cov.:

show subpopulations

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

show subpopulations

African (AFR)

AF:

0.218

AC:

2105

AN:

9640

American (AMR)

AF:

0.453

AC:

6587

AN:

14544

Ashkenazi Jewish (ASJ)

AF:

0.485

AC:

6098

AN:

12584

East Asian (EAS)

AF:

0.184

AC:

4750

AN:

25844

South Asian (SAS)

AF:

0.470

AC:

19542

AN:

41616

European-Finnish (FIN)

AF:

0.491

AC:

14061

AN:

28652

Middle Eastern (MID)

AF:

0.448

AC:

824

AN:

1838

European-Non Finnish (NFE)

AF:

0.534

AC:

133720

AN:

250198

Other (OTH)

AF:

0.458

AC:

10975

AN:

23960

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.506

Heterozygous variant carriers

4713

9425

14138

18850

23563

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

476

952

1428

1904

2380

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.423

AC:

60148

AN:

142226

Hom.:

14210

Cov.:

AF XY:

0.421

AC XY:

28987

AN XY:

68848

show subpopulations

African (AFR)

AF:

0.218

AC:

8313

AN:

38134

American (AMR)

AF:

0.460

AC:

6500

AN:

14136

Ashkenazi Jewish (ASJ)

AF:

0.497

AC:

1682

AN:

3386

East Asian (EAS)

AF:

0.146

AC:

655

AN:

4476

South Asian (SAS)

AF:

0.471

AC:

1986

AN:

4214

European-Finnish (FIN)

AF:

0.509

AC:

4768

AN:

9366

Middle Eastern (MID)

AF:

0.417

AC:

115

AN:

276

European-Non Finnish (NFE)

AF:

0.535

AC:

35013

AN:

65496

Other (OTH)

AF:

0.412

AC:

777

AN:

1888

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.505

Heterozygous variant carriers

1497

2995

4492

5990

7487

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

550

1100

1650

2200

2750

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

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 v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.76

CADD

Benign

(source)

DANN

Benign

0.85

PhyloP100

1.5

PromoterAI

-0.016

Neutral

(source)

Splicing

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over