rs12728900

Variant names:

• chr1-26420316-G-A
• rs12728900
• NM_024674.6:c.229-4987G>A

Your query was ambiguous. Multiple possible variants found:

• chr1-26420316-G-A
• chr1-26420316-G-T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_024674.6(LIN28A):​c.229-4987G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.281 in 151,802 control chromosomes in the GnomAD database, including 6,720 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 0.28 (6720 hom., cov: 30)
• Consequence: LIN28A NM_024674.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.30
• Publications: 18 publications found

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]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.414 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LIN28A	NM_024674.6	c.229-4987G>A		intron_variant	Intron 2 of 3	ENST00000326279.11	NP_078950.1
LIN28A	XM_011542148.3	c.229-4987G>A		intron_variant	Intron 2 of 4		XP_011540450.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
LIN28A	ENST00000326279.11	c.229-4987G>A		intron_variant	Intron 2 of 3	1	NM_024674.6	ENSP00000363314.3
LIN28A	ENST00000254231.4	c.229-4987G>A		intron_variant	Intron 2 of 4	1		ENSP00000254231.4

Frequencies

GnomAD3 genomes AF: 0.281 AC: 42625 AN: 151684 Hom.: 6709 Cov.: 30

Gnomad AFR AF: 0.419

Gnomad AMI AF: 0.153

Gnomad AMR AF: 0.211

Gnomad ASJ AF: 0.198

Gnomad EAS AF: 0.138

Gnomad SAS AF: 0.179

Gnomad FIN AF: 0.198

Gnomad MID AF: 0.342

Gnomad NFE AF: 0.250

Gnomad OTH AF: 0.277

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.281 AC: 42682 AN: 151802 Hom.: 6720 Cov.: 30 AF XY: 0.275 AC XY: 20401 AN XY: 74170

African (AFR) AF: 0.419 AC: 17338 AN: 41368

American (AMR) AF: 0.211 AC: 3211 AN: 15236

Ashkenazi Jewish (ASJ) AF: 0.198 AC: 687 AN: 3470

East Asian (EAS) AF: 0.138 AC: 713 AN: 5152

South Asian (SAS) AF: 0.179 AC: 862 AN: 4806

European-Finnish (FIN) AF: 0.198 AC: 2084 AN: 10540

Middle Eastern (MID) AF: 0.340 AC: 100 AN: 294

European-Non Finnish (NFE) AF: 0.250 AC: 16973 AN: 67918

Other (OTH) AF: 0.273 AC: 575 AN: 2110

Alfa AF: 0.254 Hom.: 8898

Bravo AF: 0.288

Asia WGS AF: 0.153 AC: 533 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.32
DANN	Benign	0.76
PhyloP100		-1.3
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs12728900; hg19: chr1-26746807;