7-22941785-T-G

Position:

• chr7-22941785-T-G

Variant summary

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

The NM_032581.4(HYCC1):​c.*3804A>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.279 in 152,010 control chromosomes in the GnomAD database, including 6,098 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.28 (6098 hom., cov: 32)
  • Failed GnomAD Quality Control
• Consequence: HYCC1 NM_032581.4 3_prime_UTR
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.172

Genes affected

HYCC1 (HGNC:24587): (hyccin PI4KA lipid kinase complex subunit 1) The protein encoded by this gene may play a part in the beta-catenin/Lef signaling pathway. Expression of this gene is down-regulated by beta-catenin. Defects in this gene are a cause of hypomyelination with congenital cataract (HCC). [provided by RefSeq, Oct 2008]

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.8).
• BP6: Variant 7-22941785-T-G is Benign according to our data. Variant chr7-22941785-T-G is described in ClinVar as [Benign]. Clinvar id is 359719.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.319 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
HYCC1	NM_032581.4	c.*3804A>C		3_prime_UTR_variant	11/11	ENST00000432176.7	NP_115970.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
HYCC1	ENST00000432176.7	c.*3804A>C		3_prime_UTR_variant	11/11	1	NM_032581.4	ENSP00000403396

Frequencies

GnomAD3 genomes AF: 0.279 AC: 42312 AN: 151892 Hom.: 6096 Cov.: 32

Gnomad AFR AF: 0.206

Gnomad AMI AF: 0.296

Gnomad AMR AF: 0.313

Gnomad ASJ AF: 0.263

Gnomad EAS AF: 0.119

Gnomad SAS AF: 0.270

Gnomad FIN AF: 0.316

Gnomad MID AF: 0.323

Gnomad NFE AF: 0.323

Gnomad OTH AF: 0.268

GnomAD4 exome Data not reliable, filtered out with message: AC0 AC: 0 AN: 0 Hom.: 0 Cov.: 0 AC XY: 0 AN XY: 0

GnomAD4 genome AF: 0.279 AC: 42337 AN: 152010 Hom.: 6098 Cov.: 32 AF XY: 0.280 AC XY: 20810 AN XY: 74282

Gnomad4 AFR AF: 0.207

Gnomad4 AMR AF: 0.313

Gnomad4 ASJ AF: 0.263

Gnomad4 EAS AF: 0.119

Gnomad4 SAS AF: 0.271

Gnomad4 FIN AF: 0.316

Gnomad4 NFE AF: 0.322

Gnomad4 OTH AF: 0.264

Alfa AF: 0.296 Hom.: 850

Bravo AF: 0.269

Asia WGS AF: 0.177 AC: 609 AN: 3440

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

Hypomyelination and Congenital Cataract Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jan 13, 2018

This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	4.7
DANN	Benign	0.67

Splicing

Name	Calibrated prediction	Score	Prediction
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

Other links and lift over

dbSNP: rs34683819; hg19: chr7-22981404;