rs314274

Variant names:

• chr6-104965057-A-C
• rs314274
• NM_001004317.4:c.198+6771A>C

Your query was ambiguous. Multiple possible variants found:

• chr6-104965057-A-C
• chr6-104965057-A-T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001004317.4(LIN28B):​c.198+6771A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.672 in 152,038 control chromosomes in the GnomAD database, including 34,417 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 0.67 (34417 hom., cov: 32)
• Consequence: LIN28B NM_001004317.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.52
• Publications: 11 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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.01).
• 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+6771A>C		intron_variant	Intron 2 of 3	ENST00000345080.5	NP_001004317.1
LIN28B	NM_001410939.1	c.222+6771A>C		intron_variant	Intron 3 of 4		NP_001397868.1
LIN28B	XM_006715477.3	c.255+6771A>C		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+6771A>C		intron_variant	Intron 2 of 3	1	NM_001004317.4	ENSP00000344401.4
LIN28B	ENST00000637759.1	c.222+6771A>C		intron_variant	Intron 3 of 4	5		ENSP00000490468.1
LIN28B	ENST00000635857.1	c.255+6771A>C		intron_variant	Intron 4 of 5	5		ENSP00000489735.1

Frequencies

GnomAD3 genomes AF: 0.672 AC: 102095 AN: 151920 Hom.: 34385 Cov.: 32

Gnomad AFR AF: 0.664

Gnomad AMI AF: 0.806

Gnomad AMR AF: 0.693

Gnomad ASJ AF: 0.721

Gnomad EAS AF: 0.696

Gnomad SAS AF: 0.717

Gnomad FIN AF: 0.675

Gnomad MID AF: 0.655

Gnomad NFE AF: 0.662

Gnomad OTH AF: 0.699

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

GnomAD4 genome AF: 0.672 AC: 102182 AN: 152038 Hom.: 34417 Cov.: 32 AF XY: 0.671 AC XY: 49872 AN XY: 74314

African (AFR) AF: 0.664 AC: 27525 AN: 41448

American (AMR) AF: 0.694 AC: 10596 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.721 AC: 2502 AN: 3470

East Asian (EAS) AF: 0.696 AC: 3597 AN: 5166

South Asian (SAS) AF: 0.716 AC: 3455 AN: 4824

European-Finnish (FIN) AF: 0.675 AC: 7130 AN: 10556

Middle Eastern (MID) AF: 0.646 AC: 190 AN: 294

European-Non Finnish (NFE) AF: 0.662 AC: 44970 AN: 67978

Other (OTH) AF: 0.702 AC: 1482 AN: 2112

Alfa AF: 0.674 Hom.: 65843

Bravo AF: 0.677

Asia WGS AF: 0.726 AC: 2520 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.81
DANN	Benign	0.62
PhyloP100		-1.5
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs314274; hg19: chr6-105412932;