6-104954208-C-A

Position:

• chr6-104954208-C-A

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_Moderate BA1

The NM_001410939.1(LIN28B):​c.34+3699C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.912 in 152,186 control chromosomes in the GnomAD database, including 63,429 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 0.91 (63429 hom., cov: 31)
• Consequence: LIN28B NM_001410939.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0240

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=-0.43).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.951 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
LIN28B	NM_001410939.1	c.34+3699C>A		intron_variant			NP_001397868.1
LIN28B	XM_006715477.3	c.67+3699C>A		intron_variant			XP_006715540.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
LIN28B	ENST00000635857.1	c.67+3699C>A		intron_variant		5		ENSP00000489735
LIN28B	ENST00000637759.1	c.34+3699C>A		intron_variant		5		ENSP00000490468

Frequencies

GnomAD3 genomes AF: 0.912 AC: 138726 AN: 152068 Hom.: 63364 Cov.: 31

Gnomad AFR AF: 0.954

Gnomad AMI AF: 0.956

Gnomad AMR AF: 0.937

Gnomad ASJ AF: 0.906

Gnomad EAS AF: 0.973

Gnomad SAS AF: 0.920

Gnomad FIN AF: 0.868

Gnomad MID AF: 0.975

Gnomad NFE AF: 0.882

Gnomad OTH AF: 0.920

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

GnomAD4 genome AF: 0.912 AC: 138850 AN: 152186 Hom.: 63429 Cov.: 31 AF XY: 0.912 AC XY: 67855 AN XY: 74408

Gnomad4 AFR AF: 0.954

Gnomad4 AMR AF: 0.937

Gnomad4 ASJ AF: 0.906

Gnomad4 EAS AF: 0.974

Gnomad4 SAS AF: 0.920

Gnomad4 FIN AF: 0.868

Gnomad4 NFE AF: 0.882

Gnomad4 OTH AF: 0.922

Alfa AF: 0.902 Hom.: 44481

Bravo AF: 0.920

Asia WGS AF: 0.941 AC: 3271 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.43
CADD	Benign	9.6
DANN	Benign	0.56

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs314279; hg19: chr6-105402083; COSMIC: COSV61493887; COSMIC: COSV61493887;