Variant 4-54049115-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -3 ACMG points: 2P and 5B. PM2BP4_StrongBP6

The NM_012110.4(CHIC2):c.175-5T>C variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000413 in 1,595,858 control chromosomes in the GnomAD database, with no homozygous occurrence. 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 (no stars).

Frequency

Genomes: 𝑓 0.00035 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00042 ( 0 hom. )

Consequence

CHIC2
NM_012110.4 splice_region, intron

Scores

Splicing: ADA: 0.00005920

Clinical Significance

Likely benign no assertion criteria provided B:1

Conservation

PhyloP100: -0.214

Variant links:

Genes affected

CHIC2 (HGNC:1935): (cysteine rich hydrophobic domain 2) This gene encodes a member of the CHIC family of proteins. The encoded protein contains a cysteine-rich hydrophobic (CHIC) motif, and is localized to vesicular structures and the plasma membrane. This gene is associated with some cases of acute myeloid leukemia. [provided by RefSeq, Jul 2008]

CHIC2 links:

ENSG00000282278 (HGNC:):

ENSG00000282278 links:

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ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -3 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.83).

BP6

Variant 4-54049115-A-G is Benign according to our data. Variant chr4-54049115-A-G is described in ClinVar as [Likely_benign]. Clinvar id is 3034507.Status of the report is no_assertion_criteria_provided, 0 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	MANE	Protein	UniProt
CHIC2	NM_012110.4 linkuse as main transcript	c.175-5T>C	splice_region_variant, intron_variant	ENST00000263921.8	NP_036242.1	Q9UKJ5
CHIC2	XM_006714037.5 linkuse as main transcript	c.175-5T>C	splice_region_variant, intron_variant		XP_006714100.1
CHIC2	XM_011534382.3 linkuse as main transcript	c.175-5T>C	splice_region_variant, intron_variant		XP_011532684.1
CHIC2	XM_047450063.1 linkuse as main transcript	c.67-5T>C	splice_region_variant, intron_variant		XP_047306019.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CHIC2	ENST00000263921.8 linkuse as main transcript	c.175-5T>C		splice_region_variant, intron_variant		1	NM_012110.4	ENSP00000263921.3		Q9UKJ5
ENSG00000282278	ENST00000507166.5 linkuse as main transcript	c.1018-225810A>G		intron_variant		2		ENSP00000423325.1		A0A0B4J203

Frequencies

GnomAD3 genomes

AF:

0.000348

AC:

AN:

152180

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000724

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000131

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.0000943

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000691

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000449

AC:

106

AN:

236340

Hom.:

AF XY:

0.000516

AC XY:

AN XY:

127896

show subpopulations

Gnomad AFR exome

AF:

0.0000642

Gnomad AMR exome

AF:

0.000195

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.000234

Gnomad NFE exome

AF:

0.000824

Gnomad OTH exome

AF:

0.000705

GnomAD4 exome

AF:

0.000420

AC:

606

AN:

1443560

Hom.:

Cov.:

AF XY:

0.000431

AC XY:

309

AN XY:

716850

show subpopulations

Gnomad4 AFR exome

AF:

0.0000925

Gnomad4 AMR exome

AF:

0.000170

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000122

Gnomad4 FIN exome

AF:

0.000264

Gnomad4 NFE exome

AF:

0.000513

Gnomad4 OTH exome

AF:

0.000235

GnomAD4 genome

AF:

0.000348

AC:

AN:

152298

Hom.:

Cov.:

AF XY:

0.000309

AC XY:

AN XY:

74478

show subpopulations

Gnomad4 AFR

AF:

0.0000722

Gnomad4 AMR

AF:

0.000131

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.0000943

Gnomad4 NFE

AF:

0.000691

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000606

Hom.:

Bravo

AF:

0.000355

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

CHIC2-related disorder

Benign:1

Likely benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Mar 14, 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

-0.83

CADD

Benign

8.2

DANN

Benign

0.79

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.000059

dbscSNV1_RF

Benign

0.010

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