1-226233021-A-G

Variant names:

• chr1-226233021-A-G
• rs2306119
• ENST00000481685.1:c.*71T>C

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 4 publications found

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

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
LIN9	NM_001366245.2	c.1523+75T>C		intron_variant	Intron 14 of 14	ENST00000681046.1	NP_001353174.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
LIN9	ENST00000681046.1	c.1523+75T>C		intron_variant	Intron 14 of 14		NM_001366245.2	ENSP00000505590.1

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

African (AFR) AF: 0.378 AC: 6369 AN: 16866

American (AMR) AF: 0.465 AC: 10929 AN: 23480

Ashkenazi Jewish (ASJ) AF: 0.397 AC: 6477 AN: 16318

East Asian (EAS) AF: 0.552 AC: 18854 AN: 34166

South Asian (SAS) AF: 0.298 AC: 15258 AN: 51164

European-Finnish (FIN) AF: 0.466 AC: 22563 AN: 48410

Middle Eastern (MID) AF: 0.333 AC: 1014 AN: 3042

European-Non Finnish (NFE) AF: 0.417 AC: 200021 AN: 480182

Other (OTH) AF: 0.407 AC: 13792 AN: 33928

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

African (AFR) AF: 0.377 AC: 15611 AN: 41462

American (AMR) AF: 0.429 AC: 6556 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.403 AC: 1398 AN: 3468

East Asian (EAS) AF: 0.529 AC: 2739 AN: 5176

South Asian (SAS) AF: 0.286 AC: 1379 AN: 4824

European-Finnish (FIN) AF: 0.474 AC: 5002 AN: 10552

Middle Eastern (MID) AF: 0.361 AC: 106 AN: 294

European-Non Finnish (NFE) AF: 0.416 AC: 28270 AN: 67974

Other (OTH) AF: 0.377 AC: 795 AN: 2110

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
PhyloP100		-0.76
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: rs2306119; hg19: chr1-226420722; COSMIC: COSV60244679;