NM_001004317.4:c.199-30115C>T

Variant names:

• chr6-104996183-C-T
• rs369065
• NM_001004317.4:c.199-30115C>T

Variant summary

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

The NM_001004317.4(LIN28B):​c.199-30115C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.629 in 151,954 control chromosomes in the GnomAD database, including 30,430 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 0.63 (30430 hom., cov: 31)
• Consequence: LIN28B NM_001004317.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.747
• Publications: 21 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=-0.89).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.691 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001004317.4. 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_001004317.4	MANE Select	c.199-30115C>T		intron	N/A	NP_001004317.1	Q6ZN17-1
	LIN28B	NM_001410939.1		c.223-30115C>T		intron	N/A	NP_001397868.1	A0A1B0GVD3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LIN28B	ENST00000345080.5	TSL:1 MANE Select	c.199-30115C>T		intron	N/A	ENSP00000344401.4	Q6ZN17-1
	LIN28B	ENST00000637759.1	TSL:5	c.223-30115C>T		intron	N/A	ENSP00000490468.1	A0A1B0GVD3
	LIN28B	ENST00000635857.1	TSL:5	c.256-30115C>T		intron	N/A	ENSP00000489735.1	A0A1B0GTK2

Frequencies

GnomAD3 genomes AF: 0.629 AC: 95470 AN: 151840 Hom.: 30405 Cov.: 31

Gnomad AFR AF: 0.534

Gnomad AMI AF: 0.806

Gnomad AMR AF: 0.677

Gnomad ASJ AF: 0.716

Gnomad EAS AF: 0.614

Gnomad SAS AF: 0.712

Gnomad FIN AF: 0.652

Gnomad MID AF: 0.646

Gnomad NFE AF: 0.659

Gnomad OTH AF: 0.666

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

GnomAD4 genome AF: 0.629 AC: 95542 AN: 151954 Hom.: 30430 Cov.: 31 AF XY: 0.629 AC XY: 46689 AN XY: 74266

African (AFR) AF: 0.534 AC: 22101 AN: 41414

American (AMR) AF: 0.677 AC: 10324 AN: 15256

Ashkenazi Jewish (ASJ) AF: 0.716 AC: 2481 AN: 3466

East Asian (EAS) AF: 0.615 AC: 3173 AN: 5160

South Asian (SAS) AF: 0.711 AC: 3423 AN: 4812

European-Finnish (FIN) AF: 0.652 AC: 6885 AN: 10560

Middle Eastern (MID) AF: 0.636 AC: 187 AN: 294

European-Non Finnish (NFE) AF: 0.659 AC: 44819 AN: 67968

Other (OTH) AF: 0.670 AC: 1414 AN: 2112

Alfa AF: 0.659 Hom.: 106297

Bravo AF: 0.629

Asia WGS AF: 0.686 AC: 2381 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.68
DANN	Benign	0.44
PhyloP100		-0.75
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: rs369065; hg19: chr6-105444058;