1-26417596-T-C

Variant names:

• chr1-26417596-T-C
• rs11581746
• NM_024674.6:c.228+6014T>C

Variant summary

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

The NM_024674.6(LIN28A):​c.228+6014T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.135 in 152,190 control chromosomes in the GnomAD database, including 1,615 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 0.14 (1615 hom., cov: 32)
• Consequence: LIN28A NM_024674.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.359
• Publications: 10 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=-0.91).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.177 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LIN28A	NM_024674.6	c.228+6014T>C		intron_variant	Intron 2 of 3	ENST00000326279.11	NP_078950.1
LIN28A	XM_011542148.3	c.228+6014T>C		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.228+6014T>C		intron_variant	Intron 2 of 3	1	NM_024674.6	ENSP00000363314.3
LIN28A	ENST00000254231.4	c.228+6014T>C		intron_variant	Intron 2 of 4	1		ENSP00000254231.4

Frequencies

GnomAD3 genomes AF: 0.135 AC: 20534 AN: 152072 Hom.: 1614 Cov.: 32

Gnomad AFR AF: 0.0822

Gnomad AMI AF: 0.104

Gnomad AMR AF: 0.121

Gnomad ASJ AF: 0.146

Gnomad EAS AF: 0.0135

Gnomad SAS AF: 0.0706

Gnomad FIN AF: 0.157

Gnomad MID AF: 0.222

Gnomad NFE AF: 0.180

Gnomad OTH AF: 0.144

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

GnomAD4 genome AF: 0.135 AC: 20552 AN: 152190 Hom.: 1615 Cov.: 32 AF XY: 0.132 AC XY: 9833 AN XY: 74408

African (AFR) AF: 0.0823 AC: 3418 AN: 41552

American (AMR) AF: 0.121 AC: 1848 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.146 AC: 506 AN: 3472

East Asian (EAS) AF: 0.0137 AC: 71 AN: 5190

South Asian (SAS) AF: 0.0713 AC: 344 AN: 4826

European-Finnish (FIN) AF: 0.157 AC: 1655 AN: 10570

Middle Eastern (MID) AF: 0.224 AC: 66 AN: 294

European-Non Finnish (NFE) AF: 0.180 AC: 12249 AN: 67990

Other (OTH) AF: 0.142 AC: 300 AN: 2110

Alfa AF: 0.164 Hom.: 3406

Bravo AF: 0.132

Asia WGS AF: 0.0450 AC: 159 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	2.3
DANN	Benign	0.51
PhyloP100		-0.36
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: rs11581746; hg19: chr1-26744087;