chr6-104958150-C-A

Variant names:

• chr6-104958150-C-A
• NM_001004317.4:c.62C>A

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.62C>A​(p.Ala21Glu) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: LIN28B NM_001004317.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.81
• 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=0.11068502).

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.62C>A	p.Ala21Glu	missense	Exon 2 of 4	NP_001004317.1	Q6ZN17-1
	LIN28B	NM_001410939.1		c.86C>A	p.Ala29Glu	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.62C>A	p.Ala21Glu	missense	Exon 2 of 4	ENSP00000344401.4	Q6ZN17-1
	LIN28B	ENST00000637759.1	TSL:5	c.86C>A	p.Ala29Glu	missense	Exon 3 of 5	ENSP00000490468.1	A0A1B0GVD3
	LIN28B	ENST00000635857.1	TSL:5	c.119C>A	p.Ala40Glu	missense	Exon 4 of 6	ENSP00000489735.1	A0A1B0GTK2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.078
BayesDel_addAF	Benign	-0.22	T
BayesDel_noAF	Benign	-0.56
CADD	Benign	19
DANN	Benign	0.92
DEOGEN2	Benign	0.017	T
Eigen	Benign	-0.38
Eigen_PC	Benign	-0.16
FATHMM_MKL	Benign	0.27	N
LIST_S2	Benign	0.77	T
M_CAP	Benign	0.0011	T
MetaRNN	Benign	0.11	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	-0.69	N
PhyloP100		3.8
PrimateAI	Benign	0.38	T
PROVEAN	Benign	-0.94	N
REVEL	Benign	0.21
Sift	Benign	0.34	T
Sift4G	Benign	0.89	T
Polyphen		0.0	B
Vest4		0.17
MutPred		0.23		Gain of solvent accessibility (P = 0.0068)
MVP		0.17
MPC		0.69
ClinPred		0.67	D
GERP RS		3.4
Varity_R		0.16
gMVP		0.17
Mutation Taster		=69/31	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.070		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

hg19: chr6-105406025;