chr6-104956323-G-A

Variant names:

• chr6-104956323-G-A
• rs12194974
• NM_001410939.1:c.35-1776G>A

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_Moderate BA1

The NM_001410939.1(LIN28B):​c.35-1776G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0893 in 152,090 control chromosomes in the GnomAD database, including 765 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 0.089 (765 hom., cov: 31)
• Consequence: LIN28B NM_001410939.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.37
• Publications: 12 publications found

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

Our verdict: Benign. The variant received -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.44).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.129 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LIN28B	NM_001410939.1	c.35-1776G>A		intron_variant	Intron 2 of 4		NP_001397868.1
LIN28B	XM_006715477.3	c.68-1776G>A		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.35-1776G>A		intron_variant	Intron 2 of 4	5		ENSP00000490468.1
LIN28B	ENST00000635857.1	c.68-1776G>A		intron_variant	Intron 3 of 5	5		ENSP00000489735.1

Frequencies

GnomAD3 genomes AF: 0.0894 AC: 13592 AN: 151972 Hom.: 764 Cov.: 31

Gnomad AFR AF: 0.0414

Gnomad AMI AF: 0.237

Gnomad AMR AF: 0.0712

Gnomad ASJ AF: 0.0703

Gnomad EAS AF: 0.000966

Gnomad SAS AF: 0.0432

Gnomad FIN AF: 0.0892

Gnomad MID AF: 0.0981

Gnomad NFE AF: 0.132

Gnomad OTH AF: 0.0986

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

GnomAD4 genome AF: 0.0893 AC: 13589 AN: 152090 Hom.: 765 Cov.: 31 AF XY: 0.0852 AC XY: 6332 AN XY: 74346

African (AFR) AF: 0.0413 AC: 1713 AN: 41516

American (AMR) AF: 0.0711 AC: 1088 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.0703 AC: 244 AN: 3470

East Asian (EAS) AF: 0.000968 AC: 5 AN: 5166

South Asian (SAS) AF: 0.0428 AC: 206 AN: 4816

European-Finnish (FIN) AF: 0.0892 AC: 942 AN: 10560

Middle Eastern (MID) AF: 0.0952 AC: 28 AN: 294

European-Non Finnish (NFE) AF: 0.132 AC: 8942 AN: 67954

Other (OTH) AF: 0.0975 AC: 206 AN: 2112

Alfa AF: 0.114 Hom.: 2250

Bravo AF: 0.0871

Asia WGS AF: 0.0210 AC: 72 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.44
CADD	Benign	18
DANN	Benign	0.85
PhyloP100		2.4

Splicing

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

Other links and lift over

dbSNP: rs12194974; hg19: chr6-105404198;