chr6-104958399-A-C

Variant names:

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

Variant summary

Our verdict is Benign. Variant got -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

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 -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LIN28B	NM_001004317.4	c.198+113A>C		intron_variant	Intron 2 of 3	ENST00000345080.5	NP_001004317.1
LIN28B	NM_001410939.1	c.222+113A>C		intron_variant	Intron 3 of 4		NP_001397868.1
LIN28B	XM_006715477.3	c.255+113A>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+113A>C		intron_variant	Intron 2 of 3	1	NM_001004317.4	ENSP00000344401.4
LIN28B	ENST00000637759.1	c.222+113A>C		intron_variant	Intron 3 of 4	5		ENSP00000490468.1
LIN28B	ENST00000635857.1	c.255+113A>C		intron_variant	Intron 4 of 5	5		ENSP00000489735.1

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

Gnomad4 AFR exome AF: 0.105

Gnomad4 AMR exome AF: 0.0655

Gnomad4 ASJ exome AF: 0.101

Gnomad4 EAS exome AF: 0.000388

Gnomad4 SAS exome AF: 0.0951

Gnomad4 FIN exome AF: 0.0929

Gnomad4 NFE exome AF: 0.0983

Gnomad4 OTH exome AF: 0.0928

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

Gnomad4 AFR AF: 0.112

Gnomad4 AMR AF: 0.0817

Gnomad4 ASJ AF: 0.0983

Gnomad4 EAS AF: 0.000772

Gnomad4 SAS AF: 0.0990

Gnomad4 FIN AF: 0.0979

Gnomad4 NFE AF: 0.102

Gnomad4 OTH AF: 0.0942

Alfa AF: 0.102 Hom.: 1111

Bravo AF: 0.100

Asia WGS AF: 0.0380 AC: 133 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.73
CADD	Benign	7.9
DANN	Benign	0.50

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: rs17065417; hg19: chr6-105406274;