6-104957240-C-T

Variant names:

• chr6-104957240-C-T
• rs76300431
• NM_001004317.4:c.-11C>T

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 2 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 -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.28).
• BS1: Variant frequency is greater than expected in population afr. GnomAdExome4 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 GnomAdExome4. There are 315 alleles in the male GnomAdExome4 subpopulation. Median coverage is 30. This position passed quality control check.
• BS2: High AC in GnomAd4 at 677 AD gene.

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.-11C>T		5_prime_UTR_premature_start_codon_gain	Exon 1 of 4	NP_001004317.1	Q6ZN17-1
	LIN28B	NM_001004317.4	MANE Select	c.-11C>T		5_prime_UTR	Exon 1 of 4	NP_001004317.1	Q6ZN17-1
	LIN28B	NM_001410939.1		c.35-859C>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.-11C>T		5_prime_UTR_premature_start_codon_gain	Exon 1 of 4	ENSP00000344401.4	Q6ZN17-1
	LIN28B	ENST00000345080.5	TSL:1 MANE Select	c.-11C>T		5_prime_UTR	Exon 1 of 4	ENSP00000344401.4	Q6ZN17-1
	LIN28B	ENST00000637759.1	TSL:5	c.35-859C>T		intron	N/A	ENSP00000490468.1	A0A1B0GVD3

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

GnomAD2 exomes AF: 0.00121 AC: 302 AN: 250566 AF XY: 0.000982

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 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

African (AFR) AF: 0.0184 AC: 616 AN: 33396

American (AMR) AF: 0.000673 AC: 30 AN: 44594

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26094

East Asian (EAS) AF: 0.00 AC: 0 AN: 39658

South Asian (SAS) AF: 0.0000464 AC: 4 AN: 86202

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53412

Middle Eastern (MID) AF: 0.000694 AC: 4 AN: 5760

European-Non Finnish (NFE) AF: 0.0000243 AC: 27 AN: 1111034

Other (OTH) AF: 0.000912 AC: 55 AN: 60316

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

African (AFR) AF: 0.0156 AC: 646 AN: 41514

American (AMR) AF: 0.00157 AC: 24 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5186

South Asian (SAS) AF: 0.000208 AC: 1 AN: 4812

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10620

Middle Eastern (MID) AF: 0.00340 AC: 1 AN: 294

European-Non Finnish (NFE) AF: 0.0000294 AC: 2 AN: 68012

Other (OTH) AF: 0.00142 AC: 3 AN: 2112

Alfa AF: 0.00476 Hom.: 1

Bravo AF: 0.00539

Asia WGS AF: 0.00144 AC: 5 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.28
CADD	Benign	15
DANN	Benign	0.90
PhyloP100		1.7
PromoterAI		0.016	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Mutation Taster		=292/8	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: rs76300431; hg19: chr6-105405115;