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GeneBe

1-26411441-C-G

Variant summary

Our verdict is Benign. Variant got -15 ACMG points: 0P and 15B. BP4_StrongBP6_ModerateBP7BS1BS2

The NM_024674.6(LIN28A):c.87C>G(p.Ala29=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00252 in 1,608,954 control chromosomes in the GnomAD database, including 99 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.014 ( 47 hom., cov: 32)
Exomes 𝑓: 0.0014 ( 52 hom. )

Consequence

LIN28A
NM_024674.6 synonymous

Scores

2

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 1.37
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]

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -15 ACMG points.

BP4
?
    BP4 - Multiple lines of computational evidence suggest no impact on gene or gene product (conservation, evolutionary, splicing impact, etc.)
Computational evidence support a benign effect (BayesDel_noAF=-0.49).
BP6
?
    BP6 - Reputable source recently reports variant as benign, but the evidence is not available to the laboratory to perform an independent evaluation
Variant 1-26411441-C-G is Benign according to our data. Variant chr1-26411441-C-G is described in ClinVar as [Benign]. Clinvar id is 711821.Status of the report is criteria_provided_single_submitter, 1 stars.
BP7
?
    BP7 - A synonymous (silent) variant for which splicing prediction algorithms predict no impact to the splice consensus sequence nor the creation of a new splice site AND the nucleotide is not highly conserved
Synonymous conserved (PhyloP=1.37 with no splicing effect.
BS1
?
    BS1 - Allele frequency is greater than expected for disorder
Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.0136 (2074/152322) while in subpopulation AFR AF= 0.0477 (1982/41590). AF 95% confidence interval is 0.0459. There are 47 homozygotes in gnomad4. There are 1015 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
BS2
?
    BS2 - Observed in a healthy adult individual for a recessive (homozygous), dominant (heterozygous), or X-linked (hemizygous) disorder, with full penetrance expected at an early age
High AC in GnomAd at 2074 AD gene.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
LIN28ANM_024674.6 linkuse as main transcriptc.87C>G p.Ala29= synonymous_variant 2/4 ENST00000326279.11
LIN28AXM_011542148.3 linkuse as main transcriptc.87C>G p.Ala29= synonymous_variant 2/5

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
LIN28AENST00000326279.11 linkuse as main transcriptc.87C>G p.Ala29= synonymous_variant 2/41 NM_024674.6 P1
LIN28AENST00000254231.4 linkuse as main transcriptc.87C>G p.Ala29= synonymous_variant 2/51 P1

Frequencies

GnomAD3 genomes
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.0136
AC:
2074
AN:
152204
Hom.:
47
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.0478
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00445
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.000207
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.000103
Gnomad OTH
AF:
0.00764
GnomAD3 exomes
AF:
0.00329
AC:
769
AN:
233766
Hom.:
14
AF XY:
0.00251
AC XY:
322
AN XY:
128486
show subpopulations
Gnomad AFR exome
AF:
0.0481
Gnomad AMR exome
AF:
0.00245
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.0000332
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.0000970
Gnomad OTH exome
AF:
0.00174
GnomAD4 exome
AF:
0.00136
AC:
1981
AN:
1456632
Hom.:
52
Cov.:
32
AF XY:
0.00114
AC XY:
823
AN XY:
724290
show subpopulations
Gnomad4 AFR exome
AF:
0.0499
Gnomad4 AMR exome
AF:
0.00271
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.0000233
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.0000342
Gnomad4 OTH exome
AF:
0.00255
GnomAD4 genome
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.0136
AC:
2074
AN:
152322
Hom.:
47
Cov.:
32
AF XY:
0.0136
AC XY:
1015
AN XY:
74476
show subpopulations
Gnomad4 AFR
AF:
0.0477
Gnomad4 AMR
AF:
0.00444
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.000207
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.000103
Gnomad4 OTH
AF:
0.00756
Alfa
AF:
0.00414
Hom.:
6
Bravo
AF:
0.0157
Asia WGS
AF:
0.00202
AC:
7
AN:
3478

ClinVar

Significance: Benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not provided Benign:1
Benign, criteria provided, single submitterclinical testingInvitaeMar 29, 2018- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.49
Cadd
Benign
9.0
Dann
Benign
0.60

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs116719577; hg19: chr1-26737932; API