Variant chr2-96344101-T-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

The NM_015341.5(NCAPH):c.596-4T>G variant causes a splice region, splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00264 in 1,609,008 control chromosomes in the GnomAD database, including 11 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 Likely benign (★).

Frequency

Genomes: 𝑓 0.0015 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0028 ( 11 hom. )

Consequence

NCAPH
NM_015341.5 splice_region, splice_polypyrimidine_tract, intron

Scores

Splicing: ADA: 0.0001592

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.234

Variant links:

Genes affected

NCAPH (HGNC:1112): (non-SMC condensin I complex subunit H) This gene encodes a member of the barr gene family and a regulatory subunit of the condensin complex. This complex is required for the conversion of interphase chromatin into condensed chromosomes. The protein encoded by this gene is associated with mitotic chromosomes, except during the early phase of chromosome condensation. During interphase, the protein has a distinct punctate nucleolar localization. Alternatively spliced transcript variants encoding different proteins have been described. [provided by RefSeq, Jul 2013]

NCAPH links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -10 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.7).

BP6

Variant 2-96344101-T-G is Benign according to our data. Variant chr2-96344101-T-G is described in ClinVar as [Likely_benign]. Clinvar id is 3041518.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr2-96344101-T-G is described in Lovd as [Likely_benign].

BS2

High Homozygotes in GnomAdExome4 at 11 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NCAPH	NM_015341.5 linkuse as main transcript	c.596-4T>G		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		ENST00000240423.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NCAPH	ENST00000240423.9 linkuse as main transcript	c.596-4T>G		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		1	NM_015341.5	P2	Q15003-1

Frequencies

GnomAD3 genomes

AF:

0.00148

AC:

225

AN:

152236

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000675

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000131

Gnomad ASJ

AF:

0.000288

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.0000942

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00282

Gnomad OTH

AF:

0.000478

GnomAD3 exomes

AF:

0.00120

AC:

294

AN:

245980

Hom.:

AF XY:

0.00119

AC XY:

158

AN XY:

133202

show subpopulations

Gnomad AFR exome

AF:

0.000495

Gnomad AMR exome

AF:

0.000122

Gnomad ASJ exome

AF:

0.000307

Gnomad EAS exome

AF:

0.0000553

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.000372

Gnomad NFE exome

AF:

0.00236

Gnomad OTH exome

AF:

0.000833

GnomAD4 exome

AF:

0.00276

AC:

4021

AN:

1456654

Hom.:

Cov.:

AF XY:

0.00269

AC XY:

1949

AN XY:

724802

show subpopulations

Gnomad4 AFR exome

AF:

0.000575

Gnomad4 AMR exome

AF:

0.000186

Gnomad4 ASJ exome

AF:

0.000193

Gnomad4 EAS exome

AF:

0.0000252

Gnomad4 SAS exome

AF:

0.0000235

Gnomad4 FIN exome

AF:

0.000450

Gnomad4 NFE exome

AF:

0.00350

Gnomad4 OTH exome

AF:

0.00123

GnomAD4 genome

AF:

0.00148

AC:

225

AN:

152354

Hom.:

Cov.:

AF XY:

0.00136

AC XY:

101

AN XY:

74496

show subpopulations

Gnomad4 AFR

AF:

0.000673

Gnomad4 AMR

AF:

0.000131

Gnomad4 ASJ

AF:

0.000288

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.0000942

Gnomad4 NFE

AF:

0.00282

Gnomad4 OTH

AF:

0.000473

Alfa

AF:

0.00233

Hom.:

Bravo

AF:

0.00141

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

NCAPH-related disorder

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

May 16, 2019

This variant is classified as likely 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

-0.70

CADD

Benign

7.9

DANN

Benign

0.86

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.00016

dbscSNV1_RF

Benign

0.0040

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