rs7367845

Variant names:

• chr1-226257827-C-A
• rs7367845
• NM_001366245.2:c.1039-6908G>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001366245.2(LIN9):​c.1039-6908G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.399 in 151,994 control chromosomes in the GnomAD database, including 12,315 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 0.40 (12315 hom., cov: 32)
• Consequence: LIN9 NM_001366245.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.136
• Publications: 11 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=-0.91).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.46 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LIN9	NM_001366245.2	c.1039-6908G>T		intron_variant	Intron 10 of 14	ENST00000681046.1	NP_001353174.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
LIN9	ENST00000681046.1	c.1039-6908G>T		intron_variant	Intron 10 of 14		NM_001366245.2	ENSP00000505590.1

Frequencies

GnomAD3 genomes AF: 0.399 AC: 60617 AN: 151874 Hom.: 12313 Cov.: 32

Gnomad AFR AF: 0.370

Gnomad AMI AF: 0.425

Gnomad AMR AF: 0.419

Gnomad ASJ AF: 0.387

Gnomad EAS AF: 0.476

Gnomad SAS AF: 0.265

Gnomad FIN AF: 0.463

Gnomad MID AF: 0.354

Gnomad NFE AF: 0.407

Gnomad OTH AF: 0.374

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.399 AC: 60637 AN: 151994 Hom.: 12315 Cov.: 32 AF XY: 0.400 AC XY: 29736 AN XY: 74284

African (AFR) AF: 0.370 AC: 15319 AN: 41448

American (AMR) AF: 0.420 AC: 6409 AN: 15268

Ashkenazi Jewish (ASJ) AF: 0.387 AC: 1341 AN: 3466

East Asian (EAS) AF: 0.476 AC: 2465 AN: 5178

South Asian (SAS) AF: 0.264 AC: 1271 AN: 4808

European-Finnish (FIN) AF: 0.463 AC: 4886 AN: 10560

Middle Eastern (MID) AF: 0.350 AC: 103 AN: 294

European-Non Finnish (NFE) AF: 0.407 AC: 27678 AN: 67952

Other (OTH) AF: 0.369 AC: 777 AN: 2108

Alfa AF: 0.399 Hom.: 18005

Bravo AF: 0.398

Asia WGS AF: 0.319 AC: 1108 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	1.8
DANN	Benign	0.14
PhyloP100		0.14
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: rs7367845; hg19: chr1-226445528;