15-67254963-C-A

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

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
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.365

Genes affected

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

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]

ACMG classification

Verdict is Benign. Variant got -14 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_single_submitter, 1 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	c.51+16C>A		intron_variant		ENST00000335894.9

Ensembl

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

Frequencies

GnomAD3 genomes AF: 0.209 AC: 31800 AN: 152006 Hom.: 4051 Cov.: 32

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

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.: 31 AF XY: 0.244 AC XY: 176504 AN XY: 723706

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.: 32 AF XY: 0.214 AC XY: 15896 AN XY: 74364

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:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Nov 10, 2018

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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

Other links and lift over

dbSNP: rs3743347; hg19: chr15-67547301;