6-104959787-A-C

Position:

• chr6-104959787-A-C

Variant summary

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

The NM_001004317.4(LIN28B):​c.198+1501A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.787 in 152,012 control chromosomes in the GnomAD database, including 48,143 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 0.79 (48143 hom., cov: 32)
• Consequence: LIN28B NM_001004317.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.560

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=-0.46).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.938 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
LIN28B	NM_001004317.4	c.198+1501A>C		intron_variant		ENST00000345080.5	NP_001004317.1
LIN28B	NM_001410939.1	c.222+1501A>C		intron_variant			NP_001397868.1
LIN28B	XM_006715477.3	c.255+1501A>C		intron_variant			XP_006715540.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
LIN28B	ENST00000345080.5	c.198+1501A>C		intron_variant		1	NM_001004317.4	ENSP00000344401	P1
LIN28B	ENST00000635857.1	c.255+1501A>C		intron_variant		5		ENSP00000489735
LIN28B	ENST00000637759.1	c.222+1501A>C		intron_variant		5		ENSP00000490468

Frequencies

GnomAD3 genomes AF: 0.787 AC: 119614 AN: 151894 Hom.: 48121 Cov.: 32

Gnomad AFR AF: 0.603

Gnomad AMI AF: 0.955

Gnomad AMR AF: 0.867

Gnomad ASJ AF: 0.849

Gnomad EAS AF: 0.960

Gnomad SAS AF: 0.859

Gnomad FIN AF: 0.833

Gnomad MID AF: 0.782

Gnomad NFE AF: 0.850

Gnomad OTH AF: 0.810

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

GnomAD4 genome AF: 0.787 AC: 119684 AN: 152012 Hom.: 48143 Cov.: 32 AF XY: 0.789 AC XY: 58614 AN XY: 74314

Gnomad4 AFR AF: 0.603

Gnomad4 AMR AF: 0.867

Gnomad4 ASJ AF: 0.849

Gnomad4 EAS AF: 0.961

Gnomad4 SAS AF: 0.858

Gnomad4 FIN AF: 0.833

Gnomad4 NFE AF: 0.850

Gnomad4 OTH AF: 0.812

Alfa AF: 0.847 Hom.: 105797

Bravo AF: 0.784

Asia WGS AF: 0.883 AC: 3070 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.46
CADD	Benign	16
DANN	Benign	0.83

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: rs314277; hg19: chr6-105407662;