rs314280

Positions:

• chr6-104952962-A-G
• chr6-104952962-A-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001410939.1(LIN28B):​c.34+2453A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.47 in 152,056 control chromosomes in the GnomAD database, including 18,602 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 0.47 (18602 hom., cov: 33)
• Consequence: LIN28B NM_001410939.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.546

Genes affected

LIN28B (HGNC:32207): (lin-28 homolog B) The protein encoded by this gene belongs to the lin-28 family, which is characterized by the presence of a cold-shock domain and a pair of CCHC zinc finger domains. This gene is highly expressed in testis, fetal liver, placenta, and in primary human tumors and cancer cell lines. It is negatively regulated by microRNAs that target sites in the 3' UTR, and overexpression of this gene in primary tumors is linked to the repression of let-7 family of microRNAs and derepression of let-7 targets, which facilitates cellular transformation. [provided by RefSeq, Jun 2012]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.73).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.675 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
LIN28B	NM_001410939.1	c.34+2453A>G		intron_variant			NP_001397868.1
LIN28B	XM_006715477.3	c.67+2453A>G		intron_variant			XP_006715540.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
LIN28B	ENST00000635857.1	c.67+2453A>G		intron_variant		5		ENSP00000489735
LIN28B	ENST00000637759.1	c.34+2453A>G		intron_variant		5		ENSP00000490468

Frequencies

GnomAD3 genomes AF: 0.471 AC: 71490 AN: 151938 Hom.: 18589 Cov.: 33

Gnomad AFR AF: 0.227

Gnomad AMI AF: 0.597

Gnomad AMR AF: 0.583

Gnomad ASJ AF: 0.578

Gnomad EAS AF: 0.693

Gnomad SAS AF: 0.591

Gnomad FIN AF: 0.558

Gnomad MID AF: 0.500

Gnomad NFE AF: 0.545

Gnomad OTH AF: 0.527

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

GnomAD4 genome AF: 0.470 AC: 71523 AN: 152056 Hom.: 18602 Cov.: 33 AF XY: 0.474 AC XY: 35222 AN XY: 74342

Gnomad4 AFR AF: 0.227

Gnomad4 AMR AF: 0.583

Gnomad4 ASJ AF: 0.578

Gnomad4 EAS AF: 0.694

Gnomad4 SAS AF: 0.590

Gnomad4 FIN AF: 0.558

Gnomad4 NFE AF: 0.545

Gnomad4 OTH AF: 0.532

Alfa AF: 0.546 Hom.: 36563

Bravo AF: 0.464

Asia WGS AF: 0.653 AC: 2269 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.73
CADD	Benign	0.88
DANN	Benign	0.37

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs314280; hg19: chr6-105400837;