rs6598964

Variant names:

• chr1-26419836-A-G
• rs6598964
• NM_024674.6:c.229-5467A>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.229-5467A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.661 in 152,004 control chromosomes in the GnomAD database, including 33,891 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 0.66 (33891 hom., cov: 31)
• Consequence: LIN28A NM_024674.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.280
• Publications: 13 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=-0.9).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.767 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LIN28A	NM_024674.6	c.229-5467A>G		intron_variant	Intron 2 of 3	ENST00000326279.11	NP_078950.1
LIN28A	XM_011542148.3	c.229-5467A>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.229-5467A>G		intron_variant	Intron 2 of 3	1	NM_024674.6	ENSP00000363314.3
LIN28A	ENST00000254231.4	c.229-5467A>G		intron_variant	Intron 2 of 4	1		ENSP00000254231.4

Frequencies

GnomAD3 genomes AF: 0.660 AC: 100318 AN: 151884 Hom.: 33845 Cov.: 31

Gnomad AFR AF: 0.774

Gnomad AMI AF: 0.547

Gnomad AMR AF: 0.665

Gnomad ASJ AF: 0.575

Gnomad EAS AF: 0.313

Gnomad SAS AF: 0.629

Gnomad FIN AF: 0.593

Gnomad MID AF: 0.573

Gnomad NFE AF: 0.637

Gnomad OTH AF: 0.627

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

GnomAD4 genome AF: 0.661 AC: 100418 AN: 152004 Hom.: 33891 Cov.: 31 AF XY: 0.657 AC XY: 48816 AN XY: 74292

African (AFR) AF: 0.774 AC: 32097 AN: 41468

American (AMR) AF: 0.665 AC: 10154 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.575 AC: 1993 AN: 3464

East Asian (EAS) AF: 0.312 AC: 1613 AN: 5170

South Asian (SAS) AF: 0.630 AC: 3035 AN: 4816

European-Finnish (FIN) AF: 0.593 AC: 6258 AN: 10552

Middle Eastern (MID) AF: 0.571 AC: 168 AN: 294

European-Non Finnish (NFE) AF: 0.637 AC: 43287 AN: 67948

Other (OTH) AF: 0.623 AC: 1315 AN: 2110

Alfa AF: 0.639 Hom.: 62553

Bravo AF: 0.666

Asia WGS AF: 0.449 AC: 1565 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	2.0
DANN	Benign	0.48
PhyloP100		-0.28
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: rs6598964; hg19: chr1-26746327;