NM_001004317.4:c.342C>G

Variant names:

• chr6-105026441-C-G
• NM_001004317.4:c.342C>G

Variant summary

Our verdict is Likely benign. Variant got -1 ACMG points: 2P and 3B. PM2 BP4_Moderate BP7

The NM_001004317.4(LIN28B):​c.342C>G​(p.Pro114Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000688 in 1,453,892 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. P114P) has been classified as Benign.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.9e-7 (0 hom.)
• Consequence: LIN28B NM_001004317.4 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.717

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

Verdict is Likely_benign. Variant got -1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.39).
• BP7: Synonymous conserved (PhyloP=0.717 with no splicing effect.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LIN28B	NM_001004317.4	c.342C>G	p.Pro114Pro	synonymous_variant	Exon 3 of 4	ENST00000345080.5	NP_001004317.1
LIN28B	NM_001410939.1	c.366C>G	p.Pro122Pro	synonymous_variant	Exon 4 of 5		NP_001397868.1
LIN28B	XM_006715477.3	c.399C>G	p.Pro133Pro	synonymous_variant	Exon 4 of 5		XP_006715540.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
LIN28B	ENST00000345080.5	c.342C>G	p.Pro114Pro	synonymous_variant	Exon 3 of 4	1	NM_001004317.4	ENSP00000344401.4
LIN28B	ENST00000637759.1	c.366C>G	p.Pro122Pro	synonymous_variant	Exon 4 of 5	5		ENSP00000490468.1
LIN28B	ENST00000635857.1	c.399C>G	p.Pro133Pro	synonymous_variant	Exon 5 of 6	5		ENSP00000489735.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.88e-7 AC: 1 AN: 1453892 Hom.: 0 Cov.: 29 AF XY: 0.00000138 AC XY: 1 AN XY: 723260

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000118

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.39
CADD	Benign	7.1
DANN	Benign	0.65
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr6-105474316;