6-104958128-C-T

Variant names:

• chr6-104958128-C-T
• rs1407660834
• NM_001004317.4:c.40C>T

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001004317.4(LIN28B):​c.40C>T​(p.Pro14Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000689 in 1,450,834 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. P14A) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 31)
  • Exomes 𝑓: 6.9e-7 (0 hom.)
• Consequence: LIN28B NM_001004317.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.90
• Publications: 0 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]

ENSG00000308685 (HGNC:):

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.19945869).

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.40C>T	p.Pro14Ser	missense	Exon 2 of 4	NP_001004317.1	Q6ZN17-1
	LIN28B	NM_001410939.1		c.64C>T	p.Pro22Ser	missense	Exon 3 of 5	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.40C>T	p.Pro14Ser	missense	Exon 2 of 4	ENSP00000344401.4	Q6ZN17-1
	LIN28B	ENST00000637759.1	TSL:5	c.64C>T	p.Pro22Ser	missense	Exon 3 of 5	ENSP00000490468.1	A0A1B0GVD3
	LIN28B	ENST00000635857.1	TSL:5	c.97C>T	p.Pro33Ser	missense	Exon 4 of 6	ENSP00000489735.1	A0A1B0GTK2

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome AF: 6.89e-7 AC: 1 AN: 1450834 Hom.: 0 Cov.: 32 AF XY: 0.00000139 AC XY: 1 AN XY: 720288

African (AFR) AF: 0.00 AC: 0 AN: 33370

American (AMR) AF: 0.00 AC: 0 AN: 44542

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25960

East Asian (EAS) AF: 0.00 AC: 0 AN: 39456

South Asian (SAS) AF: 0.00 AC: 0 AN: 84730

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53186

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5540

European-Non Finnish (NFE) AF: 9.06e-7 AC: 1 AN: 1104222

Other (OTH) AF: 0.00 AC: 0 AN: 59828

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.091
BayesDel_addAF	Benign	-0.11	T
BayesDel_noAF	Benign	-0.40
CADD	Benign	17
DANN	Uncertain	0.99
DEOGEN2	Benign	0.024	T
Eigen	Benign	0.010
Eigen_PC	Benign	0.15
FATHMM_MKL	Uncertain	0.84	D
LIST_S2	Uncertain	0.91	D
M_CAP	Benign	0.0023	T
MetaRNN	Benign	0.20	T
MetaSVM	Benign	-0.89	T
MutationAssessor	Uncertain	2.2	M
PhyloP100		1.9
PrimateAI	Benign	0.48	T
PROVEAN	Benign	-1.2	N
REVEL	Benign	0.20
Sift	Uncertain	0.0090	D
Sift4G	Benign	0.073	T
Polyphen		0.10	B
Vest4		0.25
MutPred		0.23		Gain of phosphorylation at P14 (P = 0.0037)
MVP		0.21
MPC		0.60
ClinPred		0.92	D
GERP RS		4.9
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.081
gMVP		0.23
Mutation Taster		=79/21	polymorphism

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: rs1407660834; hg19: chr6-105406003;