6-104995314-T-A

Position:

• chr6-104995314-T-A

Variant summary

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

The NM_001004317.4(LIN28B):​c.199-30984T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.479 in 151,852 control chromosomes in the GnomAD database, including 19,302 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 0.48 (19302 hom., cov: 31)
• Consequence: LIN28B NM_001004317.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.743

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=-0.92).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.672 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
LIN28B	NM_001004317.4	c.199-30984T>A		intron_variant		ENST00000345080.5	NP_001004317.1
LIN28B	NM_001410939.1	c.223-30984T>A		intron_variant			NP_001397868.1
LIN28B	XM_006715477.3	c.256-30984T>A		intron_variant			XP_006715540.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
LIN28B	ENST00000345080.5	c.199-30984T>A		intron_variant		1	NM_001004317.4	ENSP00000344401.4
LIN28B	ENST00000637759.1	c.223-30984T>A		intron_variant		5		ENSP00000490468.1
LIN28B	ENST00000635857.1	c.256-30984T>A		intron_variant		5		ENSP00000489735.1

Frequencies

GnomAD3 genomes AF: 0.479 AC: 72693 AN: 151734 Hom.: 19292 Cov.: 31

Gnomad AFR AF: 0.228

Gnomad AMI AF: 0.668

Gnomad AMR AF: 0.580

Gnomad ASJ AF: 0.620

Gnomad EAS AF: 0.691

Gnomad SAS AF: 0.590

Gnomad FIN AF: 0.578

Gnomad MID AF: 0.535

Gnomad NFE AF: 0.558

Gnomad OTH AF: 0.541

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

GnomAD4 genome AF: 0.479 AC: 72724 AN: 151852 Hom.: 19302 Cov.: 31 AF XY: 0.483 AC XY: 35824 AN XY: 74220

Gnomad4 AFR AF: 0.228

Gnomad4 AMR AF: 0.580

Gnomad4 ASJ AF: 0.620

Gnomad4 EAS AF: 0.691

Gnomad4 SAS AF: 0.589

Gnomad4 FIN AF: 0.578

Gnomad4 NFE AF: 0.558

Gnomad4 OTH AF: 0.546

Alfa AF: 0.502 Hom.: 2433

Bravo AF: 0.470

Asia WGS AF: 0.656 AC: 2277 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	3.5
DANN	Benign	0.55

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: rs364663; hg19: chr6-105443189;