Genetic Variant NM_001004317.4:c.*1430T>A (chr6-105080213-T-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_001004317.4(LIN28B):c.*1430T>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.521 in 151,802 control chromosomes in the GnomAD database, including 21,762 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 0.52 ( 21694 hom., cov: 30)

Exomes 𝑓: 0.55 ( 68 hom. )

Consequence

LIN28B
NM_001004317.4 3_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.368

Publications

17 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=-0.84).

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.617 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001004317.4. 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
	LIN28B	NM_001004317.4	MANE Select	c.*1430T>A		3_prime_UTR	Exon 4 of 4	NP_001004317.1
	LIN28B	NM_001410939.1		c.*1430T>A		3_prime_UTR	Exon 5 of 5	NP_001397868.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LIN28B	ENST00000345080.5	TSL:1 MANE Select	c.*1430T>A		3_prime_UTR	Exon 4 of 4	ENSP00000344401.4
	LIN28B	ENST00000637759.1	TSL:5	c.*1430T>A		3_prime_UTR	Exon 5 of 5	ENSP00000490468.1

Frequencies

GnomAD3 genomes

AF:

0.521

AC:

78766

AN:

151246

Hom.:

21679

Cov.:

show subpopulations

Gnomad AFR

AF:

0.331

Gnomad AMI

AF:

0.678

Gnomad AMR

AF:

0.513

Gnomad ASJ

AF:

0.619

Gnomad EAS

AF:

0.434

Gnomad SAS

AF:

0.614

Gnomad FIN

AF:

0.573

Gnomad MID

AF:

0.525

Gnomad NFE

AF:

0.622

Gnomad OTH

AF:

0.563

GnomAD4 exome

AF:

0.546

AC:

239

AN:

438

Hom.:

Cov.:

AF XY:

0.538

AC XY:

143

AN XY:

266

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:

0.549

AC:

234

AN:

426

Middle Eastern (MID)

AC:

AN:

European-Non Finnish (NFE)

AF:

0.375

AC:

AN:

Other (OTH)

AF:

0.500

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.439

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.521

AC:

78800

AN:

151364

Hom.:

21694

Cov.:

AF XY:

0.518

AC XY:

38305

AN XY:

73894

show subpopulations

African (AFR)

AF:

0.330

AC:

13628

AN:

41266

American (AMR)

AF:

0.513

AC:

7789

AN:

15192

Ashkenazi Jewish (ASJ)

AF:

0.619

AC:

2147

AN:

3468

East Asian (EAS)

AF:

0.434

AC:

2233

AN:

5144

South Asian (SAS)

AF:

0.613

AC:

2938

AN:

4790

European-Finnish (FIN)

AF:

0.573

AC:

5979

AN:

10430

Middle Eastern (MID)

AF:

0.527

AC:

155

AN:

294

European-Non Finnish (NFE)

AF:

0.622

AC:

42122

AN:

67770

Other (OTH)

AF:

0.568

AC:

1193

AN:

2102

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.476

Heterozygous variant carriers

1589

3177

4766

6354

7943

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

692

1384

2076

2768

3460

<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:

0.555

Hom.:

2881

Bravo

AF:

0.508

Asia WGS

AF:

0.568

AC:

1971

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.84

CADD

Benign

2.6

(source)

DANN

Benign

0.71

PhyloP100

0.37

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