rs7532866

Variant names:

• chr1-26415053-A-G
• rs7532866
• NM_024674.6:c.228+3471A>G

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+3471A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.357 in 152,018 control chromosomes in the GnomAD database, including 9,919 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 0.36 (9919 hom., cov: 32)
• Consequence: LIN28A NM_024674.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.72
• Publications: 32 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=-0.8).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.394 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LIN28A	NM_024674.6	c.228+3471A>G		intron_variant	Intron 2 of 3	ENST00000326279.11	NP_078950.1
LIN28A	XM_011542148.3	c.228+3471A>G		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+3471A>G		intron_variant	Intron 2 of 3	1	NM_024674.6	ENSP00000363314.3
LIN28A	ENST00000254231.4	c.228+3471A>G		intron_variant	Intron 2 of 4	1		ENSP00000254231.4

Frequencies

GnomAD3 genomes AF: 0.357 AC: 54230 AN: 151898 Hom.: 9912 Cov.: 32

Gnomad AFR AF: 0.399

Gnomad AMI AF: 0.270

Gnomad AMR AF: 0.376

Gnomad ASJ AF: 0.349

Gnomad EAS AF: 0.134

Gnomad SAS AF: 0.395

Gnomad FIN AF: 0.349

Gnomad MID AF: 0.215

Gnomad NFE AF: 0.346

Gnomad OTH AF: 0.322

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

GnomAD4 genome AF: 0.357 AC: 54266 AN: 152018 Hom.: 9919 Cov.: 32 AF XY: 0.357 AC XY: 26534 AN XY: 74300

African (AFR) AF: 0.399 AC: 16518 AN: 41430

American (AMR) AF: 0.375 AC: 5733 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.349 AC: 1210 AN: 3470

East Asian (EAS) AF: 0.134 AC: 692 AN: 5174

South Asian (SAS) AF: 0.396 AC: 1906 AN: 4808

European-Finnish (FIN) AF: 0.349 AC: 3684 AN: 10550

Middle Eastern (MID) AF: 0.211 AC: 62 AN: 294

European-Non Finnish (NFE) AF: 0.346 AC: 23537 AN: 67990

Other (OTH) AF: 0.321 AC: 678 AN: 2114

Alfa AF: 0.340 Hom.: 28167

Bravo AF: 0.354

Asia WGS AF: 0.252 AC: 877 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	12
DANN	Benign	0.68
PhyloP100		1.7
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: rs7532866; hg19: chr1-26741544;