rs221634

Positions:

• chr6-105080213-T-A
• chr6-105080213-T-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001004317.4(LIN28B):​c.*1430T>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.521 in 151,802 control chromosomes in the GnomAD database, including 21,762 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 0.52 (21694 hom., cov: 30)
  • Exomes 𝑓: 0.55 (68 hom.)
• Consequence: LIN28B NM_001004317.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.368

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.617 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
LIN28B	NM_001004317.4	c.*1430T>A		3_prime_UTR_variant	4/4	ENST00000345080.5
LIN28B	NM_001410939.1	c.*1430T>A		3_prime_UTR_variant	5/5
LIN28B	XM_006715477.3	c.*1430T>A		3_prime_UTR_variant	5/5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
LIN28B	ENST00000345080.5	c.*1430T>A		3_prime_UTR_variant	4/4	1	NM_001004317.4	P1
LIN28B	ENST00000637759.1	c.*1430T>A		3_prime_UTR_variant	5/5	5

Frequencies

GnomAD3 genomes AF: 0.521 AC: 78766 AN: 151246 Hom.: 21679 Cov.: 30

Gnomad AFR AF: 0.331

Gnomad AMI AF: 0.678

Gnomad AMR AF: 0.513

Gnomad ASJ AF: 0.619

Gnomad EAS AF: 0.434

Gnomad SAS AF: 0.614

Gnomad FIN AF: 0.573

Gnomad MID AF: 0.525

Gnomad NFE AF: 0.622

Gnomad OTH AF: 0.563

GnomAD4 exome AF: 0.546 AC: 239 AN: 438 Hom.: 68 Cov.: 0 AF XY: 0.538 AC XY: 143 AN XY: 266

Gnomad4 FIN exome AF: 0.549

Gnomad4 NFE exome AF: 0.375

Gnomad4 OTH exome AF: 0.500

GnomAD4 genome AF: 0.521 AC: 78800 AN: 151364 Hom.: 21694 Cov.: 30 AF XY: 0.518 AC XY: 38305 AN XY: 73894

Gnomad4 AFR AF: 0.330

Gnomad4 AMR AF: 0.513

Gnomad4 ASJ AF: 0.619

Gnomad4 EAS AF: 0.434

Gnomad4 SAS AF: 0.613

Gnomad4 FIN AF: 0.573

Gnomad4 NFE AF: 0.622

Gnomad4 OTH AF: 0.568

Alfa AF: 0.555 Hom.: 2881

Bravo AF: 0.508

Asia WGS AF: 0.568 AC: 1971 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	2.6
DANN	Benign	0.71

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: rs221634; hg19: chr6-105528088; COSMIC: COSV61497783; COSMIC: COSV61497783;