6-104952962-A-G

Variant names:

• chr6-104952962-A-G
• rs314280
• NM_001410939.1:c.34+2453A>G

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 65 publications found

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

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001410939.1. 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
	LIN28B	NM_001410939.1		c.34+2453A>G		intron	N/A	NP_001397868.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LIN28B	ENST00000637759.1	TSL:5	c.34+2453A>G		intron	N/A	ENSP00000490468.1
	LIN28B	ENST00000635857.1	TSL:5	c.67+2453A>G		intron	N/A	ENSP00000489735.1

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

African (AFR) AF: 0.227 AC: 9417 AN: 41476

American (AMR) AF: 0.583 AC: 8914 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.578 AC: 2005 AN: 3470

East Asian (EAS) AF: 0.694 AC: 3580 AN: 5162

South Asian (SAS) AF: 0.590 AC: 2850 AN: 4828

European-Finnish (FIN) AF: 0.558 AC: 5899 AN: 10566

Middle Eastern (MID) AF: 0.493 AC: 145 AN: 294

European-Non Finnish (NFE) AF: 0.545 AC: 37049 AN: 67958

Other (OTH) AF: 0.532 AC: 1122 AN: 2110

Alfa AF: 0.533 Hom.: 81919

Bravo AF: 0.464

Asia WGS AF: 0.653 AC: 2269 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.73
CADD	Benign	0.88
DANN	Benign	0.37
PhyloP100		-0.55

Splicing

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

Other links and lift over

dbSNP: rs314280; hg19: chr6-105400837;