Genetic Variant LIN28B:c.*3016C>T (chr6-105081799-C-T) – ACMG Classification: Benign (-12 pts)

Variant summary

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

The ENST00000345080.5(LIN28B):c.*3016C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.782 in 152,568 control chromosomes in the GnomAD database, including 47,550 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 0.78 ( 47404 hom., cov: 31)

Exomes 𝑓: 0.80 ( 146 hom. )

Consequence

LIN28B
ENST00000345080.5 3_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.554

Publications

13 publications found

Variant links:

Genes affected

LIN28B (HGNC:32207): (lin-28 homolog B) The protein encoded by this gene belongs to the lin-28 family, which is characterized by the presence of a cold-shock domain and a pair of CCHC zinc finger domains. This gene is highly expressed in testis, fetal liver, placenta, and in primary human tumors and cancer cell lines. It is negatively regulated by microRNAs that target sites in the 3' UTR, and overexpression of this gene in primary tumors is linked to the repression of let-7 family of microRNAs and derepression of let-7 targets, which facilitates cellular transformation. [provided by RefSeq, Jun 2012]

LIN28B 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=-0.66).

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.861 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000345080.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LIN28B	NM_001004317.4	MANE Select	c.*3016C>T		3_prime_UTR	Exon 4 of 4	NP_001004317.1
	LIN28B	NM_001410939.1		c.*3016C>T		3_prime_UTR	Exon 5 of 5	NP_001397868.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LIN28B	ENST00000345080.5	TSL:1 MANE Select	c.*3016C>T		3_prime_UTR	Exon 4 of 4	ENSP00000344401.4

Frequencies

GnomAD3 genomes

AF:

0.782

AC:

118841

AN:

152002

Hom.:

47391

Cov.:

show subpopulations

Gnomad AFR

AF:

0.614

Gnomad AMI

AF:

0.918

Gnomad AMR

AF:

0.789

Gnomad ASJ

AF:

0.852

Gnomad EAS

AF:

0.820

Gnomad SAS

AF:

0.853

Gnomad FIN

AF:

0.792

Gnomad MID

AF:

0.759

Gnomad NFE

AF:

0.867

Gnomad OTH

AF:

0.804

GnomAD4 exome

AF:

0.801

AC:

359

AN:

448

Hom.:

146

Cov.:

AF XY:

0.818

AC XY:

224

AN XY:

274

show subpopulations

African (AFR)

AF:

1.00

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:

0.794

AC:

327

AN:

412

Middle Eastern (MID)

AC:

AN:

European-Non Finnish (NFE)

AF:

0.893

AC:

AN:

Other (OTH)

AF:

0.833

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.484

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.782

AC:

118901

AN:

152120

Hom.:

47404

Cov.:

AF XY:

0.779

AC XY:

57916

AN XY:

74358

show subpopulations

African (AFR)

AF:

0.613

AC:

25419

AN:

41448

American (AMR)

AF:

0.789

AC:

12076

AN:

15296

Ashkenazi Jewish (ASJ)

AF:

0.852

AC:

2959

AN:

3472

East Asian (EAS)

AF:

0.820

AC:

4235

AN:

5164

South Asian (SAS)

AF:

0.853

AC:

4112

AN:

4820

European-Finnish (FIN)

AF:

0.792

AC:

8389

AN:

10592

Middle Eastern (MID)

AF:

0.769

AC:

226

AN:

294

European-Non Finnish (NFE)

AF:

0.867

AC:

58945

AN:

68010

Other (OTH)

AF:

0.807

AC:

1705

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

1264

2529

3793

5058

6322

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

866

1732

2598

3464

4330

<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:

0.828

Hom.:

20957

Bravo

AF:

0.774

Asia WGS

AF:

0.824

AC:

2869

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.66

CADD

Benign

9.1

(source)

DANN

Benign

0.66

PhyloP100

0.55

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.0

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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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over