rs11247955

Variant names:

• chr1-26421717-G-A
• rs11247955
• NM_024674.6:c.229-3586G>A

Variant summary

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

The NM_024674.6(LIN28A):​c.229-3586G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.431 in 151,830 control chromosomes in the GnomAD database, including 15,489 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 0.43 (15489 hom., cov: 32)
• Consequence: LIN28A NM_024674.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.164
• Publications: 8 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 = 0.528 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LIN28A	NM_024674.6	c.229-3586G>A		intron_variant	Intron 2 of 3	ENST00000326279.11	NP_078950.1
LIN28A	XM_011542148.3	c.229-3586G>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.229-3586G>A		intron_variant	Intron 2 of 3	1	NM_024674.6	ENSP00000363314.3
LIN28A	ENST00000254231.4	c.229-3586G>A		intron_variant	Intron 2 of 4	1		ENSP00000254231.4

Frequencies

GnomAD3 genomes AF: 0.431 AC: 65431 AN: 151712 Hom.: 15487 Cov.: 32

Gnomad AFR AF: 0.268

Gnomad AMI AF: 0.434

Gnomad AMR AF: 0.471

Gnomad ASJ AF: 0.562

Gnomad EAS AF: 0.103

Gnomad SAS AF: 0.340

Gnomad FIN AF: 0.516

Gnomad MID AF: 0.491

Gnomad NFE AF: 0.532

Gnomad OTH AF: 0.441

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

GnomAD4 genome AF: 0.431 AC: 65472 AN: 151830 Hom.: 15489 Cov.: 32 AF XY: 0.429 AC XY: 31823 AN XY: 74198

African (AFR) AF: 0.268 AC: 11105 AN: 41372

American (AMR) AF: 0.471 AC: 7194 AN: 15268

Ashkenazi Jewish (ASJ) AF: 0.562 AC: 1949 AN: 3470

East Asian (EAS) AF: 0.103 AC: 535 AN: 5174

South Asian (SAS) AF: 0.342 AC: 1645 AN: 4812

European-Finnish (FIN) AF: 0.516 AC: 5416 AN: 10492

Middle Eastern (MID) AF: 0.486 AC: 143 AN: 294

European-Non Finnish (NFE) AF: 0.532 AC: 36167 AN: 67934

Other (OTH) AF: 0.439 AC: 924 AN: 2106

Alfa AF: 0.501 Hom.: 25792

Bravo AF: 0.422

Asia WGS AF: 0.228 AC: 795 AN: 3472

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	1.2
DANN	Benign	0.71
PhyloP100		-0.16
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: rs11247955; hg19: chr1-26748208;