Variant 15-67254963-C-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_001031715.3(IQCH):c.51+16C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.239 in 1,607,192 control chromosomes in the GnomAD database, including 49,564 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.21 ( 4053 hom., cov: 32)

Exomes 𝑓: 0.24 ( 45511 hom. )

Consequence

IQCH
NM_001031715.3 intron

Scores

Clinical Significance

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

Conservation

PhyloP100: -0.365

Variant links:

Genes affected

IQCH (HGNC:25721): (IQ motif containing H)

IQCH links:

AAGAB (HGNC:25662): (alpha and gamma adaptin binding protein) The protein encoded by this gene interacts with the gamma-adaptin and alpha-adaptin subunits of complexes involved in clathrin-coated vesicle trafficking. Mutations in this gene are associated with type I punctate palmoplantar keratoderma. Alternatively spliced transcript variants have been found for this gene. [provided by RefSeq, Dec 2012]

AAGAB links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.79).

BP6

Variant 15-67254963-C-A is Benign according to our data. Variant chr15-67254963-C-A is described in ClinVar as [Benign]. Clinvar id is 1235883.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.453 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
IQCH	NM_001031715.3 linkuse as main transcript	c.51+16C>A		intron_variant		ENST00000335894.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
IQCH	ENST00000335894.9 linkuse as main transcript	c.51+16C>A		intron_variant		1	NM_001031715.3	A2	Q86VS3-1

Frequencies

GnomAD3 genomes

AF:

0.209

AC:

31800

AN:

152006

Hom.:

4051

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0862

Gnomad AMI

AF:

0.212

Gnomad AMR

AF:

0.321

Gnomad ASJ

AF:

0.364

Gnomad EAS

AF:

0.468

Gnomad SAS

AF:

0.297

Gnomad FIN

AF:

0.182

Gnomad MID

AF:

0.317

Gnomad NFE

AF:

0.228

Gnomad OTH

AF:

0.246

GnomAD3 exomes

AF:

0.262

AC:

63719

AN:

242988

Hom.:

9173

AF XY:

0.261

AC XY:

34403

AN XY:

131588

show subpopulations

Gnomad AFR exome

AF:

0.0787

Gnomad AMR exome

AF:

0.363

Gnomad ASJ exome

AF:

0.361

Gnomad EAS exome

AF:

0.467

Gnomad SAS exome

AF:

0.284

Gnomad FIN exome

AF:

0.170

Gnomad NFE exome

AF:

0.228

Gnomad OTH exome

AF:

0.260

GnomAD4 exome

AF:

0.242

AC:

352806

AN:

1455068

Hom.:

45511

Cov.:

AF XY:

0.244

AC XY:

176504

AN XY:

723706

show subpopulations

Gnomad4 AFR exome

AF:

0.0807

Gnomad4 AMR exome

AF:

0.358

Gnomad4 ASJ exome

AF:

0.363

Gnomad4 EAS exome

AF:

0.483

Gnomad4 SAS exome

AF:

0.292

Gnomad4 FIN exome

AF:

0.172

Gnomad4 NFE exome

AF:

0.230

Gnomad4 OTH exome

AF:

0.247

GnomAD4 genome

AF:

0.209

AC:

31821

AN:

152124

Hom.:

4053

Cov.:

AF XY:

0.214

AC XY:

15896

AN XY:

74364

show subpopulations

Gnomad4 AFR

AF:

0.0861

Gnomad4 AMR

AF:

0.322

Gnomad4 ASJ

AF:

0.364

Gnomad4 EAS

AF:

0.469

Gnomad4 SAS

AF:

0.297

Gnomad4 FIN

AF:

0.182

Gnomad4 NFE

AF:

0.228

Gnomad4 OTH

AF:

0.247

Alfa

AF:

0.181

Hom.:

683

Bravo

AF:

0.215

Asia WGS

AF:

0.355

AC:

1234

AN:

3478

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	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Nov 10, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.79

CADD

Benign

2.9

DANN

Benign

0.52

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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