1-26429718-G-T

Variant names:

• chr1-26429718-G-T
• rs6697410
• ENST00000254231.4:c.*2752G>T

Variant summary

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

The ENST00000254231.4(LIN28A):​c.*2752G>T variant causes a splice region change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.787 in 152,188 control chromosomes in the GnomAD database, including 47,405 homozygotes. In-silico tool predicts a benign outcome for this variant. 1/1 splice prediction tools predict no significant impact on normal splicing. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.79 (47402 hom., cov: 32)
  • Exomes 𝑓: 1.0 (3 hom.)
• Consequence: LIN28A ENST00000254231.4 splice_region
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.284
• Publications: 23 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]

DHDDS-AS1 (HGNC:40925): (DHDDS antisense RNA 1)

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.63).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.858 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000254231.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LIN28A	NM_024674.6	MANE Select	c.*3260G>T		3_prime_UTR	Exon 4 of 4	NP_078950.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LIN28A	ENST00000254231.4	TSL:1	c.*2752G>T		splice_region	Exon 5 of 5	ENSP00000254231.4
	LIN28A	ENST00000326279.11	TSL:1 MANE Select	c.*3260G>T		3_prime_UTR	Exon 4 of 4	ENSP00000363314.3
	LIN28A	ENST00000254231.4	TSL:1	c.*2752G>T		3_prime_UTR	Exon 5 of 5	ENSP00000254231.4

Frequencies

GnomAD3 genomes AF: 0.787 AC: 119686 AN: 152064 Hom.: 47361 Cov.: 32

Gnomad AFR AF: 0.838

Gnomad AMI AF: 0.662

Gnomad AMR AF: 0.852

Gnomad ASJ AF: 0.805

Gnomad EAS AF: 0.879

Gnomad SAS AF: 0.842

Gnomad FIN AF: 0.730

Gnomad MID AF: 0.823

Gnomad NFE AF: 0.740

Gnomad OTH AF: 0.787

GnomAD4 exome AF: 1.00 AC: 6 AN: 6 Hom.: 3 Cov.: 0 AF XY: 1.00 AC XY: 4 AN XY: 4

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AF: 1.00 AC: 2 AN: 2

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 1.00 AC: 4 AN: 4

Other (OTH) AC: 0 AN: 0

GnomAD4 genome AF: 0.787 AC: 119787 AN: 152182 Hom.: 47402 Cov.: 32 AF XY: 0.790 AC XY: 58739 AN XY: 74396

African (AFR) AF: 0.838 AC: 34816 AN: 41526

American (AMR) AF: 0.852 AC: 13039 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.805 AC: 2792 AN: 3470

East Asian (EAS) AF: 0.879 AC: 4564 AN: 5190

South Asian (SAS) AF: 0.842 AC: 4058 AN: 4820

European-Finnish (FIN) AF: 0.730 AC: 7725 AN: 10576

Middle Eastern (MID) AF: 0.816 AC: 240 AN: 294

European-Non Finnish (NFE) AF: 0.740 AC: 50287 AN: 67990

Other (OTH) AF: 0.788 AC: 1666 AN: 2114

Alfa AF: 0.768 Hom.: 81544

Bravo AF: 0.800

Asia WGS AF: 0.845 AC: 2938 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.63
CADD	Benign	6.5
DANN	Benign	0.85
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: rs6697410; hg19: chr1-26756209; COSMIC: COSV52578679; COSMIC: COSV52578679;