Variant 1-226233494-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -17 ACMG points: 0P and 17B. BP4_StrongBP6_Very_StrongBP7BS2

The NM_001366245.2(LIN9):c.1275A>G(p.Ala425Ala) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00583 in 1,613,920 control chromosomes in the GnomAD database, including 42 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0041 ( 4 hom., cov: 33)

Exomes 𝑓: 0.0060 ( 38 hom. )

Consequence

LIN9
NM_001366245.2 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -0.137

Variant links:

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]

LIN9 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -17 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.6).

BP6

Variant 1-226233494-T-C is Benign according to our data. Variant chr1-226233494-T-C is described in ClinVar as [Benign]. Clinvar id is 779403.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-0.137 with no splicing effect.

BS2

High Homozygotes in GnomAd4 at 4 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
LIN9	NM_001366245.2 linkuse as main transcript	c.1275A>G	p.Ala425Ala	synonymous_variant	13/15	ENST00000681046.1	NP_001353174.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
LIN9	ENST00000681046.1 linkuse as main transcript	c.1275A>G	p.Ala425Ala	synonymous_variant	13/15		NM_001366245.2	ENSP00000505590.1		Q5TKA1-1

Frequencies

GnomAD3 genomes

AF:

0.00415

AC:

631

AN:

152202

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000868

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00563

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000192

Gnomad SAS

AF:

0.00912

Gnomad FIN

AF:

0.00574

Gnomad MID

AF:

0.00633

Gnomad NFE

AF:

0.00578

Gnomad OTH

AF:

0.00382

GnomAD3 exomes

AF:

0.00498

AC:

1250

AN:

251010

Hom.:

AF XY:

0.00559

AC XY:

759

AN XY:

135674

show subpopulations

Gnomad AFR exome

AF:

0.00117

Gnomad AMR exome

AF:

0.00372

Gnomad ASJ exome

AF:

0.0000993

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00954

Gnomad FIN exome

AF:

0.00490

Gnomad NFE exome

AF:

0.00605

Gnomad OTH exome

AF:

0.00294

GnomAD4 exome

AF:

0.00601

AC:

8784

AN:

1461600

Hom.:

Cov.:

AF XY:

0.00625

AC XY:

4543

AN XY:

727090

show subpopulations

Gnomad4 AFR exome

AF:

0.000807

Gnomad4 AMR exome

AF:

0.00354

Gnomad4 ASJ exome

AF:

0.0000765

Gnomad4 EAS exome

AF:

0.0000252

Gnomad4 SAS exome

AF:

0.00976

Gnomad4 FIN exome

AF:

0.00444

Gnomad4 NFE exome

AF:

0.00641

Gnomad4 OTH exome

AF:

0.00571

GnomAD4 genome

AF:

0.00414

AC:

631

AN:

152320

Hom.:

Cov.:

AF XY:

0.00423

AC XY:

315

AN XY:

74484

show subpopulations

Gnomad4 AFR

AF:

0.000866

Gnomad4 AMR

AF:

0.00562

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.000193

Gnomad4 SAS

AF:

0.00913

Gnomad4 FIN

AF:

0.00574

Gnomad4 NFE

AF:

0.00578

Gnomad4 OTH

AF:

0.00378

Alfa

AF:

0.00471

Hom.:

Bravo

AF:

0.00411

Asia WGS

AF:

0.00433

AC:

AN:

3478

EpiCase

AF:

0.00584

EpiControl

AF:

0.00783

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Nov 09, 2018	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.60

CADD

Benign

4.1

DANN

Benign

0.67

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over