rs314276

Positions:

• chr6-104960124-A-C
• chr6-104960124-A-G

Variant summary

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

The NM_001004317.4(LIN28B):​c.198+1838A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.649 in 151,960 control chromosomes in the GnomAD database, including 32,215 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 0.65 (32215 hom., cov: 33)
• Consequence: LIN28B NM_001004317.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.87

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=-0.9).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.696 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
LIN28B	NM_001004317.4	c.198+1838A>C		intron_variant		ENST00000345080.5
LIN28B	NM_001410939.1	c.222+1838A>C		intron_variant
LIN28B	XM_006715477.3	c.255+1838A>C		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
LIN28B	ENST00000345080.5	c.198+1838A>C		intron_variant		1	NM_001004317.4	P1
LIN28B	ENST00000635857.1	c.255+1838A>C		intron_variant		5
LIN28B	ENST00000637759.1	c.222+1838A>C		intron_variant		5

Frequencies

GnomAD3 genomes AF: 0.649 AC: 98542 AN: 151840 Hom.: 32189 Cov.: 33

Gnomad AFR AF: 0.583

Gnomad AMI AF: 0.806

Gnomad AMR AF: 0.685

Gnomad ASJ AF: 0.721

Gnomad EAS AF: 0.696

Gnomad SAS AF: 0.717

Gnomad FIN AF: 0.676

Gnomad MID AF: 0.655

Gnomad NFE AF: 0.661

Gnomad OTH AF: 0.681

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.649 AC: 98622 AN: 151960 Hom.: 32215 Cov.: 33 AF XY: 0.649 AC XY: 48212 AN XY: 74266

Gnomad4 AFR AF: 0.583

Gnomad4 AMR AF: 0.685

Gnomad4 ASJ AF: 0.721

Gnomad4 EAS AF: 0.696

Gnomad4 SAS AF: 0.716

Gnomad4 FIN AF: 0.676

Gnomad4 NFE AF: 0.661

Gnomad4 OTH AF: 0.684

Alfa AF: 0.589 Hom.: 2606

Bravo AF: 0.651

Asia WGS AF: 0.717 AC: 2455 AN: 3430

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	1.7
DANN	Benign	0.85

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: rs314276; hg19: chr6-105407999;