rs76300431

Positions:

• chr6-104957240-C-T

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_Moderate BS1 BS2

The NM_001004317.4(LIN28B):​c.-11C>T variant causes a 5 prime UTR premature start codon gain change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000876 in 1,612,690 control chromosomes in the GnomAD database, including 8 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 0.0044 (3 hom., cov: 32)
  • Exomes 𝑓: 0.00050 (5 hom.)
• Consequence: LIN28B NM_001004317.4 5_prime_UTR_premature_start_codon_gain
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.73

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 Benign. Variant got -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.28).
• BS1: Variant frequency is greater than expected in population afr. gnomad4_exome allele frequency = 0.000504 (736/1460466) while in subpopulation AFR AF= 0.0184 (616/33396). AF 95% confidence interval is 0.0172. There are 5 homozygotes in gnomad4_exome. There are 315 alleles in male gnomad4_exome subpopulation. Median coverage is 30. This position pass quality control queck.
• BS2: High AC in GnomAd4 at 677 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
LIN28B	NM_001004317.4	c.-11C>T		5_prime_UTR_premature_start_codon_gain_variant	1/4	ENST00000345080.5	NP_001004317.1
LIN28B	NM_001004317.4	c.-11C>T		5_prime_UTR_variant	1/4	ENST00000345080.5	NP_001004317.1
LIN28B	NM_001410939.1	c.35-859C>T		intron_variant			NP_001397868.1
LIN28B	XM_006715477.3	c.68-859C>T		intron_variant			XP_006715540.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
LIN28B	ENST00000345080.5	c.-11C>T		5_prime_UTR_premature_start_codon_gain_variant	1/4	1	NM_001004317.4	ENSP00000344401.4
LIN28B	ENST00000345080.5	c.-11C>T		5_prime_UTR_variant	1/4	1	NM_001004317.4	ENSP00000344401.4
LIN28B	ENST00000637759.1	c.35-859C>T		intron_variant		5		ENSP00000490468.1
LIN28B	ENST00000635857.1	c.68-859C>T		intron_variant		5		ENSP00000489735.1

Frequencies

GnomAD3 genomes AF: 0.00444 AC: 675 AN: 152106 Hom.: 3 Cov.: 32

Gnomad AFR AF: 0.0156

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00157

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000208

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.0000294

Gnomad OTH AF: 0.00144

GnomAD3 exomes AF: 0.00121 AC: 302 AN: 250566 Hom.: 2 AF XY: 0.000982 AC XY: 133 AN XY: 135428

Gnomad AFR exome AF: 0.0170

Gnomad AMR exome AF: 0.000581

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000265

Gnomad OTH exome AF: 0.000490

GnomAD4 exome AF: 0.000504 AC: 736 AN: 1460466 Hom.: 5 Cov.: 30 AF XY: 0.000434 AC XY: 315 AN XY: 726584

Gnomad4 AFR exome AF: 0.0184

Gnomad4 AMR exome AF: 0.000673

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000464

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000243

Gnomad4 OTH exome AF: 0.000912

GnomAD4 genome AF: 0.00445 AC: 677 AN: 152224 Hom.: 3 Cov.: 32 AF XY: 0.00434 AC XY: 323 AN XY: 74450

Gnomad4 AFR AF: 0.0156

Gnomad4 AMR AF: 0.00157

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000208

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000294

Gnomad4 OTH AF: 0.00142

Alfa AF: 0.00203 Hom.: 1

Bravo AF: 0.00539

Asia WGS AF: 0.00144 AC: 5 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.28
CADD	Benign	15
DANN	Benign	0.90
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

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

LitVar

Other links and lift over

dbSNP: rs76300431; hg19: chr6-105405115;