6-104953138-T-G

Variant names:

• chr6-104953138-T-G
• rs9404590
• NM_001410939.1:c.34+2629T>G

Variant summary

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

The NM_001410939.1(LIN28B):​c.34+2629T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.155 in 152,142 control chromosomes in the GnomAD database, including 1,979 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 0.15 (1979 hom., cov: 32)
• Consequence: LIN28B NM_001410939.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.340

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=-0.65).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.253 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LIN28B	NM_001410939.1	c.34+2629T>G		intron_variant	Intron 2 of 4		NP_001397868.1
LIN28B	XM_006715477.3	c.67+2629T>G		intron_variant	Intron 2 of 4		XP_006715540.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
LIN28B	ENST00000637759.1	c.34+2629T>G		intron_variant	Intron 2 of 4	5		ENSP00000490468.1
LIN28B	ENST00000635857.1	c.67+2629T>G		intron_variant	Intron 3 of 5	5		ENSP00000489735.1

Frequencies

GnomAD3 genomes AF: 0.155 AC: 23523 AN: 152024 Hom.: 1978 Cov.: 32

Gnomad AFR AF: 0.115

Gnomad AMI AF: 0.149

Gnomad AMR AF: 0.159

Gnomad ASJ AF: 0.135

Gnomad EAS AF: 0.264

Gnomad SAS AF: 0.114

Gnomad FIN AF: 0.154

Gnomad MID AF: 0.127

Gnomad NFE AF: 0.174

Gnomad OTH AF: 0.144

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

GnomAD4 genome AF: 0.155 AC: 23524 AN: 152142 Hom.: 1979 Cov.: 32 AF XY: 0.155 AC XY: 11503 AN XY: 74358

Gnomad4 AFR AF: 0.115

Gnomad4 AMR AF: 0.159

Gnomad4 ASJ AF: 0.135

Gnomad4 EAS AF: 0.264

Gnomad4 SAS AF: 0.113

Gnomad4 FIN AF: 0.154

Gnomad4 NFE AF: 0.174

Gnomad4 OTH AF: 0.144

Alfa AF: 0.160 Hom.: 3410

Bravo AF: 0.154

Asia WGS AF: 0.156 AC: 544 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.65
CADD	Benign	7.0
DANN	Benign	0.54

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs9404590; hg19: chr6-105401013; COSMIC: COSV61493885; COSMIC: COSV61493885;