1-226233021-A-G

Position:

• chr1-226233021-A-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000481685.1(LIN9):​c.*71T>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.416 in 859,604 control chromosomes in the GnomAD database, including 76,206 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 0.41 (13053 hom., cov: 32)
  • Exomes 𝑓: 0.42 (63153 hom.)
• Consequence: LIN9 ENST00000481685.1 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.758

Genes affected

LIN9 (HGNC:30830): (lin-9 DREAM MuvB core complex component) This gene encodes a tumor suppressor protein that inhibits DNA synthesis and oncogenic transformation through association with the retinoblastoma 1 protein. The encoded protein also interacts with a complex of other cell cycle regulators to repress cell cycle-dependent gene expression in non-dividing cells. Alternatively spliced transcript variants encoding multiple isoforms have been observed for this gene. [provided by RefSeq, Jul 2012]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.513 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
LIN9	NM_001366245.2	c.1523+75T>C		intron_variant		ENST00000681046.1	NP_001353174.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
LIN9	ENST00000681046.1	c.1523+75T>C		intron_variant			NM_001366245.2	ENSP00000505590

Frequencies

GnomAD3 genomes AF: 0.410 AC: 62330 AN: 151930 Hom.: 13051 Cov.: 32

Gnomad AFR AF: 0.377

Gnomad AMI AF: 0.544

Gnomad AMR AF: 0.429

Gnomad ASJ AF: 0.403

Gnomad EAS AF: 0.528

Gnomad SAS AF: 0.287

Gnomad FIN AF: 0.474

Gnomad MID AF: 0.361

Gnomad NFE AF: 0.416

Gnomad OTH AF: 0.383

GnomAD4 exome AF: 0.417 AC: 295277 AN: 707556 Hom.: 63153 Cov.: 9 AF XY: 0.411 AC XY: 151781 AN XY: 369060

Gnomad4 AFR exome AF: 0.378

Gnomad4 AMR exome AF: 0.465

Gnomad4 ASJ exome AF: 0.397

Gnomad4 EAS exome AF: 0.552

Gnomad4 SAS exome AF: 0.298

Gnomad4 FIN exome AF: 0.466

Gnomad4 NFE exome AF: 0.417

Gnomad4 OTH exome AF: 0.407

GnomAD4 genome AF: 0.410 AC: 62352 AN: 152048 Hom.: 13053 Cov.: 32 AF XY: 0.412 AC XY: 30629 AN XY: 74326

Gnomad4 AFR AF: 0.377

Gnomad4 AMR AF: 0.429

Gnomad4 ASJ AF: 0.403

Gnomad4 EAS AF: 0.529

Gnomad4 SAS AF: 0.286

Gnomad4 FIN AF: 0.474

Gnomad4 NFE AF: 0.416

Gnomad4 OTH AF: 0.377

Alfa AF: 0.335 Hom.: 1255

Bravo AF: 0.409

Asia WGS AF: 0.358 AC: 1244 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	0.027
DANN	Benign	0.71

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: rs2306119; hg19: chr1-226420722; COSMIC: COSV60244679;