Variant 12-122279123-C-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -15 ACMG points: 1P and 16B. PP2BP4_StrongBP6_Very_StrongBS2

The NM_001247997.2(CLIP1):c.3670G>T(p.Ala1224Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00679 in 1,611,020 control chromosomes in the GnomAD database, including 43 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★). Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

Frequency

Genomes: 𝑓 0.0056 ( 7 hom., cov: 32)

Exomes 𝑓: 0.0069 ( 36 hom. )

Consequence

CLIP1
NM_001247997.2 missense

Scores

Clinical Significance

Likely benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -1.02

Variant links:

Genes affected

CLIP1 (HGNC:10461): (CAP-Gly domain containing linker protein 1) The protein encoded by this gene links endocytic vesicles to microtubules. This gene is highly expressed in Reed-Sternberg cells of Hodgkin disease. Several transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Oct 2011]

CLIP1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -15 ACMG points.

PP2

Missense variant in gene, where missense usually causes diseases (based on misZ statistic), CLIP1. . Trascript score misZ 3.4483 (greater than threshold 3.09). GenCC has associacion of gene with autosomal recessive non-syndromic intellectual disability, intellectual disability.

BP4

Computational evidence support a benign effect (MetaRNN=0.0024212897).

BP6

Variant 12-122279123-C-A is Benign according to our data. Variant chr12-122279123-C-A is described in ClinVar as [Likely_benign]. Clinvar id is 788442.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS2

High AC in GnomAd4 at 854 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CLIP1	NM_001247997.2 linkuse as main transcript	c.3670G>T	p.Ala1224Ser	missense_variant	22/26	ENST00000620786.5	NP_001234926.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CLIP1	ENST00000620786.5 linkuse as main transcript	c.3670G>T	p.Ala1224Ser	missense_variant	22/26	5	NM_001247997.2	ENSP00000479322	A1	P30622-3

Frequencies

GnomAD3 genomes

AF:

0.00561

AC:

854

AN:

152144

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00167

Gnomad AMI

AF:

0.00330

Gnomad AMR

AF:

0.00779

Gnomad ASJ

AF:

0.0115

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00311

Gnomad FIN

AF:

0.0000943

Gnomad MID

AF:

0.00633

Gnomad NFE

AF:

0.00876

Gnomad OTH

AF:

0.00431

GnomAD3 exomes

AF:

0.00520

AC:

1288

AN:

247854

Hom.:

AF XY:

0.00548

AC XY:

735

AN XY:

134074

show subpopulations

Gnomad AFR exome

AF:

0.00117

Gnomad AMR exome

AF:

0.00382

Gnomad ASJ exome

AF:

0.0103

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00205

Gnomad FIN exome

AF:

0.000278

Gnomad NFE exome

AF:

0.00831

Gnomad OTH exome

AF:

0.00595

GnomAD4 exome

AF:

0.00691

AC:

10083

AN:

1458758

Hom.:

Cov.:

AF XY:

0.00684

AC XY:

4965

AN XY:

725768

show subpopulations

Gnomad4 AFR exome

AF:

0.00123

Gnomad4 AMR exome

AF:

0.00366

Gnomad4 ASJ exome

AF:

0.0107

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00246

Gnomad4 FIN exome

AF:

0.000432

Gnomad4 NFE exome

AF:

0.00803

Gnomad4 OTH exome

AF:

0.00714

GnomAD4 genome

AF:

0.00561

AC:

854

AN:

152262

Hom.:

Cov.:

AF XY:

0.00502

AC XY:

374

AN XY:

74442

show subpopulations

Gnomad4 AFR

AF:

0.00166

Gnomad4 AMR

AF:

0.00778

Gnomad4 ASJ

AF:

0.0115

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00311

Gnomad4 FIN

AF:

0.0000943

Gnomad4 NFE

AF:

0.00876

Gnomad4 OTH

AF:

0.00426

Alfa

AF:

0.00815

Hom.:

Bravo

AF:

0.00595

TwinsUK

AF:

0.00890

AC:

ALSPAC

AF:

0.00675

AC:

ESP6500AA

AF:

0.00159

AC:

ESP6500EA

AF:

0.00849

AC:

ExAC

AF:

0.00488

AC:

592

Asia WGS

AF:

0.00144

AC:

AN:

3478

EpiCase

AF:

0.00966

EpiControl

AF:

0.00789

ClinVar

Significance: Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Likely benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Likely benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Dec 31, 2019	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.088

BayesDel_addAF

Benign

-0.60

BayesDel_noAF

Benign

-0.63

CADD

Benign

DANN

Benign

0.86

DEOGEN2

Benign

0.061

.;.;.;.;T;.;.;T

Eigen

Benign

-1.1

Eigen_PC

Benign

-0.98

FATHMM_MKL

Benign

0.13

LIST_S2

Benign

0.80

T;T;.;T;T;T;T;.

MetaRNN

Benign

0.0024

T;T;T;T;T;T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

-0.90

.;.;.;.;N;.;.;N

MutationTaster

Benign

1.0

N;N;N;N;N

PrimateAI

Benign

0.26

PROVEAN

Benign

-0.38

.;.;N;N;.;N;.;N

REVEL

Benign

0.029

Sift

Benign

0.18

.;.;T;T;.;T;.;T

Sift4G

Benign

0.74

T;.;T;T;T;T;.;T

Polyphen

0.011, 0.015

.;.;B;B;B;B;.;B

Vest4

0.11

MVP

0.31

MPC

0.57

ClinPred

0.0085

GERP RS

-4.1

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.025

gMVP

0.089

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

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