chr6-104958399-A-C

Variant names:

• chr6-104958399-A-C
• rs17065417
• NM_001004317.4:c.198+113A>C

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+113A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0932 in 836,690 control chromosomes in the GnomAD database, including 4,009 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 0.099 (788 hom., cov: 32)
  • Exomes 𝑓: 0.092 (3221 hom.)
• Consequence: LIN28B NM_001004317.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.47
• Publications: 35 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]

ENSG00000308685 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.73).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.11 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LIN28B	NM_001004317.4	MANE Select	c.198+113A>C		intron	N/A	NP_001004317.1	Q6ZN17-1
	LIN28B	NM_001410939.1		c.222+113A>C		intron	N/A	NP_001397868.1	A0A1B0GVD3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LIN28B	ENST00000345080.5	TSL:1 MANE Select	c.198+113A>C		intron	N/A	ENSP00000344401.4	Q6ZN17-1
	LIN28B	ENST00000637759.1	TSL:5	c.222+113A>C		intron	N/A	ENSP00000490468.1	A0A1B0GVD3
	LIN28B	ENST00000635857.1	TSL:5	c.255+113A>C		intron	N/A	ENSP00000489735.1	A0A1B0GTK2

Frequencies

GnomAD3 genomes AF: 0.0990 AC: 15056 AN: 152050 Hom.: 787 Cov.: 32

Gnomad AFR AF: 0.112

Gnomad AMI AF: 0.137

Gnomad AMR AF: 0.0819

Gnomad ASJ AF: 0.0983

Gnomad EAS AF: 0.000770

Gnomad SAS AF: 0.0983

Gnomad FIN AF: 0.0979

Gnomad MID AF: 0.114

Gnomad NFE AF: 0.102

Gnomad OTH AF: 0.0952

GnomAD4 exome AF: 0.0920 AC: 62947 AN: 684522 Hom.: 3221 AF XY: 0.0924 AC XY: 31904 AN XY: 345142

African (AFR) AF: 0.105 AC: 1886 AN: 17964

American (AMR) AF: 0.0655 AC: 1716 AN: 26212

Ashkenazi Jewish (ASJ) AF: 0.101 AC: 1443 AN: 14282

East Asian (EAS) AF: 0.000388 AC: 13 AN: 33506

South Asian (SAS) AF: 0.0951 AC: 2932 AN: 30828

European-Finnish (FIN) AF: 0.0929 AC: 2974 AN: 32012

Middle Eastern (MID) AF: 0.128 AC: 491 AN: 3822

European-Non Finnish (NFE) AF: 0.0983 AC: 48495 AN: 493586

Other (OTH) AF: 0.0928 AC: 2997 AN: 32310

GnomAD4 genome AF: 0.0990 AC: 15062 AN: 152168 Hom.: 788 Cov.: 32 AF XY: 0.0987 AC XY: 7346 AN XY: 74402

African (AFR) AF: 0.112 AC: 4663 AN: 41512

American (AMR) AF: 0.0817 AC: 1249 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.0983 AC: 341 AN: 3468

East Asian (EAS) AF: 0.000772 AC: 4 AN: 5184

South Asian (SAS) AF: 0.0990 AC: 477 AN: 4818

European-Finnish (FIN) AF: 0.0979 AC: 1037 AN: 10590

Middle Eastern (MID) AF: 0.116 AC: 34 AN: 294

European-Non Finnish (NFE) AF: 0.102 AC: 6933 AN: 67996

Other (OTH) AF: 0.0942 AC: 199 AN: 2112

Alfa AF: 0.101 Hom.: 2605

Bravo AF: 0.100

Asia WGS AF: 0.0380 AC: 133 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.73
CADD	Benign	7.9
DANN	Benign	0.50
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: rs17065417; hg19: chr6-105406274;