chr6-104970103-G-A

Variant names:

• chr6-104970103-G-A
• rs314268
• NM_001004317.4:c.198+11817G>A

Variant summary

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

The NM_001004317.4(LIN28B):​c.198+11817G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.641 in 151,966 control chromosomes in the GnomAD database, including 31,483 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 0.64 (31483 hom., cov: 31)
• Consequence: LIN28B NM_001004317.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.618

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=-0.88).
• 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 rank	MANE	Protein	UniProt
LIN28B	NM_001004317.4	c.198+11817G>A		intron_variant	Intron 2 of 3	ENST00000345080.5	NP_001004317.1
LIN28B	NM_001410939.1	c.222+11817G>A		intron_variant	Intron 3 of 4		NP_001397868.1
LIN28B	XM_006715477.3	c.255+11817G>A		intron_variant	Intron 3 of 4		XP_006715540.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
LIN28B	ENST00000345080.5	c.198+11817G>A		intron_variant	Intron 2 of 3	1	NM_001004317.4	ENSP00000344401.4
LIN28B	ENST00000637759.1	c.222+11817G>A		intron_variant	Intron 3 of 4	5		ENSP00000490468.1
LIN28B	ENST00000635857.1	c.255+11817G>A		intron_variant	Intron 4 of 5	5		ENSP00000489735.1

Frequencies

GnomAD3 genomes AF: 0.641 AC: 97297 AN: 151848 Hom.: 31459 Cov.: 31

Gnomad AFR AF: 0.558

Gnomad AMI AF: 0.805

Gnomad AMR AF: 0.680

Gnomad ASJ AF: 0.719

Gnomad EAS AF: 0.696

Gnomad SAS AF: 0.716

Gnomad FIN AF: 0.676

Gnomad MID AF: 0.649

Gnomad NFE AF: 0.660

Gnomad OTH AF: 0.671

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

GnomAD4 genome AF: 0.641 AC: 97370 AN: 151966 Hom.: 31483 Cov.: 31 AF XY: 0.641 AC XY: 47639 AN XY: 74264

Gnomad4 AFR AF: 0.558

Gnomad4 AMR AF: 0.680

Gnomad4 ASJ AF: 0.719

Gnomad4 EAS AF: 0.696

Gnomad4 SAS AF: 0.716

Gnomad4 FIN AF: 0.676

Gnomad4 NFE AF: 0.660

Gnomad4 OTH AF: 0.675

Alfa AF: 0.667 Hom.: 53903

Bravo AF: 0.640

Asia WGS AF: 0.718 AC: 2492 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	2.6
DANN	Benign	0.38

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: rs314268; hg19: chr6-105417978; COSMIC: COSV61497879;