NM_001004317.4:c.198+1501A>C

Variant names:

• chr6-104959787-A-C
• rs314277
• NM_001004317.4:c.198+1501A>C

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 70 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=-0.46).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.938 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001004317.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LIN28B	NM_001004317.4	MANE Select	c.198+1501A>C		intron	N/A	NP_001004317.1
	LIN28B	NM_001410939.1		c.222+1501A>C		intron	N/A	NP_001397868.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LIN28B	ENST00000345080.5	TSL:1 MANE Select	c.198+1501A>C		intron	N/A	ENSP00000344401.4
	LIN28B	ENST00000637759.1	TSL:5	c.222+1501A>C		intron	N/A	ENSP00000490468.1
	LIN28B	ENST00000635857.1	TSL:5	c.255+1501A>C		intron	N/A	ENSP00000489735.1

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

African (AFR) AF: 0.603 AC: 24968 AN: 41422

American (AMR) AF: 0.867 AC: 13240 AN: 15268

Ashkenazi Jewish (ASJ) AF: 0.849 AC: 2947 AN: 3472

East Asian (EAS) AF: 0.961 AC: 4974 AN: 5178

South Asian (SAS) AF: 0.858 AC: 4134 AN: 4816

European-Finnish (FIN) AF: 0.833 AC: 8806 AN: 10566

Middle Eastern (MID) AF: 0.779 AC: 229 AN: 294

European-Non Finnish (NFE) AF: 0.850 AC: 57806 AN: 67980

Other (OTH) AF: 0.812 AC: 1711 AN: 2106

Alfa AF: 0.838 Hom.: 213198

Bravo AF: 0.784

Asia WGS AF: 0.883 AC: 3070 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.46
CADD	Benign	16
DANN	Benign	0.83
PhyloP100		0.56
Mutation Taster		=98/2	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: rs314277; hg19: chr6-105407662;