rs7788668

Positions:

• chr7-22941019-C-A
• chr7-22941019-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000432176.7(HYCC1):​c.*4570G>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.276 in 151,894 control chromosomes in the GnomAD database, including 5,978 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.28 (5978 hom., cov: 30)
  • Exomes 𝑓: 0.29 (0 hom.)
• Consequence: HYCC1 ENST00000432176.7 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.217

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.316 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
HYCC1	NM_032581.4	c.*4570G>T		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.*4570G>T		3_prime_UTR_variant	11/11	1	NM_032581.4	ENSP00000403396
HYCC1	ENST00000421730.1	n.90G>T		non_coding_transcript_exon_variant	2/4	4
HYCC1	ENST00000465661.2	n.1182+19237G>T		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes AF: 0.276 AC: 41847 AN: 151762 Hom.: 5976 Cov.: 30

Gnomad AFR AF: 0.205

Gnomad AMI AF: 0.288

Gnomad AMR AF: 0.309

Gnomad ASJ AF: 0.263

Gnomad EAS AF: 0.101

Gnomad SAS AF: 0.268

Gnomad FIN AF: 0.315

Gnomad MID AF: 0.318

Gnomad NFE AF: 0.319

Gnomad OTH AF: 0.265

GnomAD4 exome AF: 0.286 AC: 4 AN: 14 Hom.: 0 Cov.: 0 AF XY: 0.200 AC XY: 2 AN XY: 10

Gnomad4 AMR exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.500

Gnomad4 NFE exome AF: 0.375

GnomAD4 genome AF: 0.276 AC: 41873 AN: 151880 Hom.: 5978 Cov.: 30 AF XY: 0.277 AC XY: 20559 AN XY: 74228

Gnomad4 AFR AF: 0.205

Gnomad4 AMR AF: 0.310

Gnomad4 ASJ AF: 0.263

Gnomad4 EAS AF: 0.101

Gnomad4 SAS AF: 0.269

Gnomad4 FIN AF: 0.315

Gnomad4 NFE AF: 0.319

Gnomad4 OTH AF: 0.261

Alfa AF: 0.302 Hom.: 14414

Bravo AF: 0.266

Asia WGS AF: 0.174 AC: 604 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	2.1
DANN	Benign	0.56

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: rs7788668; hg19: chr7-22980638;