6-104944870-C-T

Variant names:

• chr6-104944870-C-T
• rs314263
• NM_001410939.1:c.-16+3858C>T

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_Moderate BA1

The NM_001410939.1(LIN28B):​c.-16+3858C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.69 in 151,942 control chromosomes in the GnomAD database, including 36,237 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 0.69 (36237 hom., cov: 32)
• Consequence: LIN28B NM_001410939.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.89
• Publications: 38 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 -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.34).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.716 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LIN28B	NM_001410939.1		c.-16+3858C>T		intron	N/A	NP_001397868.1	A0A1B0GVD3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LIN28B	ENST00000637759.1	TSL:5	c.-16+3858C>T		intron	N/A	ENSP00000490468.1	A0A1B0GVD3
	LIN28B	ENST00000635857.1	TSL:5	c.19-5591C>T		intron	N/A	ENSP00000489735.1	A0A1B0GTK2

Frequencies

GnomAD3 genomes AF: 0.690 AC: 104776 AN: 151824 Hom.: 36195 Cov.: 32

Gnomad AFR AF: 0.689

Gnomad AMI AF: 0.806

Gnomad AMR AF: 0.727

Gnomad ASJ AF: 0.718

Gnomad EAS AF: 0.696

Gnomad SAS AF: 0.728

Gnomad FIN AF: 0.680

Gnomad MID AF: 0.646

Gnomad NFE AF: 0.678

Gnomad OTH AF: 0.705

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

GnomAD4 genome AF: 0.690 AC: 104874 AN: 151942 Hom.: 36237 Cov.: 32 AF XY: 0.689 AC XY: 51166 AN XY: 74270

African (AFR) AF: 0.689 AC: 28562 AN: 41456

American (AMR) AF: 0.728 AC: 11113 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.718 AC: 2490 AN: 3466

East Asian (EAS) AF: 0.697 AC: 3607 AN: 5178

South Asian (SAS) AF: 0.727 AC: 3505 AN: 4818

European-Finnish (FIN) AF: 0.680 AC: 7178 AN: 10556

Middle Eastern (MID) AF: 0.643 AC: 189 AN: 294

European-Non Finnish (NFE) AF: 0.678 AC: 46004 AN: 67880

Other (OTH) AF: 0.707 AC: 1491 AN: 2108

Alfa AF: 0.688 Hom.: 86965

Bravo AF: 0.697

Asia WGS AF: 0.733 AC: 2542 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.34
CADD	Benign	17
DANN	Benign	0.71
PhyloP100		2.9

Splicing

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs314263; hg19: chr6-105392745;