Variant 14-95193845-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_ModerateBP6_ModerateBS2

The NM_024734.4(CLMN):c.2840+4G>A variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000696 in 1,613,842 control chromosomes in the GnomAD database, including 13 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.0039 ( 4 hom., cov: 33)

Exomes 𝑓: 0.00036 ( 9 hom. )

Consequence

CLMN
NM_024734.4 splice_region, intron

Scores

Splicing: ADA: 0.0003097

Clinical Significance

Benign criteria provided, single submitter B:2

Conservation

PhyloP100: 0.164

Variant links:

Genes affected

CLMN (HGNC:19972): (calmin) Predicted to enable actin filament binding activity. Predicted to be involved in negative regulation of cell population proliferation and nuclear migration. Predicted to act upstream of or within neuron projection development. Predicted to be integral component of membrane. Predicted to be part of meiotic nuclear membrane microtubule tethering complex. Predicted to be active in cytoplasm and nuclear outer membrane. [provided by Alliance of Genome Resources, Apr 2022]

CLMN links:

CLMN (HGNC:):

CLMN links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -8 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.43).

BP6

Variant 14-95193845-C-T is Benign according to our data. Variant chr14-95193845-C-T is described in ClinVar as [Benign]. Clinvar id is 783696.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High Homozygotes in GnomAd4 at 4 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	MANE	Protein	UniProt
CLMN	NM_024734.4 linkuse as main transcript	c.2840+4G>A	splice_region_variant, intron_variant	ENST00000298912.9	NP_079010.2	Q96JQ2Q6NUQ2
CLMN	XM_011537158.2 linkuse as main transcript	c.2840+4G>A	splice_region_variant, intron_variant		XP_011535460.1
CLMN	XM_017021646.2 linkuse as main transcript	c.2780+4G>A	splice_region_variant, intron_variant		XP_016877135.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CLMN	ENST00000298912.9 linkuse as main transcript	c.2840+4G>A		splice_region_variant, intron_variant		1	NM_024734.4	ENSP00000298912.3		Q96JQ2

Frequencies

GnomAD3 genomes

AF:

0.00388

AC:

590

AN:

152096

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0136

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00105

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000441

Gnomad OTH

AF:

0.00384

GnomAD3 exomes

AF:

0.000971

AC:

244

AN:

251176

Hom.:

AF XY:

0.000722

AC XY:

AN XY:

135726

show subpopulations

Gnomad AFR exome

AF:

0.0135

Gnomad AMR exome

AF:

0.000551

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000328

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00000880

Gnomad OTH exome

AF:

0.000489

GnomAD4 exome

AF:

0.000363

AC:

530

AN:

1461628

Hom.:

Cov.:

AF XY:

0.000325

AC XY:

236

AN XY:

727090

show subpopulations

Gnomad4 AFR exome

AF:

0.0129

Gnomad4 AMR exome

AF:

0.000716

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000116

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000719

Gnomad4 OTH exome

AF:

0.000911

GnomAD4 genome

AF:

0.00390

AC:

593

AN:

152214

Hom.:

Cov.:

AF XY:

0.00370

AC XY:

275

AN XY:

74420

show subpopulations

Gnomad4 AFR

AF:

0.0136

Gnomad4 AMR

AF:

0.00105

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000441

Gnomad4 OTH

AF:

0.00380

Alfa

AF:

0.00200

Hom.:

Bravo

AF:

0.00478

Asia WGS

AF:

0.000289

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Aug 14, 2018

- -

CLMN-related disorder

Benign:1

Benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Jul 10, 2019

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.43

CADD

Benign

DANN

Benign

0.83

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.00031

dbscSNV1_RF

Benign

0.12

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