rs2270101

Positions:

• chr7-22896385-A-G

Variant summary

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

The XM_011515590.3(HYCC1):​c.992-267T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.397 in 152,102 control chromosomes in the GnomAD database, including 12,159 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 0.40 (12159 hom., cov: 32)
• Consequence: HYCC1 XM_011515590.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.147

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]

HYCC1 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.42 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
HYCC1	XM_011515590.3	c.992-267T>C		intron_variant			XP_011513892.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
HYCC1	ENST00000421730.1	n.138-5236T>C		intron_variant		4

Frequencies

GnomAD3 genomes AF: 0.397 AC: 60339 AN: 151982 Hom.: 12142 Cov.: 32

Gnomad AFR AF: 0.389

Gnomad AMI AF: 0.355

Gnomad AMR AF: 0.387

Gnomad ASJ AF: 0.400

Gnomad EAS AF: 0.119

Gnomad SAS AF: 0.306

Gnomad FIN AF: 0.453

Gnomad MID AF: 0.426

Gnomad NFE AF: 0.424

Gnomad OTH AF: 0.369

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.397 AC: 60393 AN: 152102 Hom.: 12159 Cov.: 32 AF XY: 0.396 AC XY: 29484 AN XY: 74366

Gnomad4 AFR AF: 0.389

Gnomad4 AMR AF: 0.387

Gnomad4 ASJ AF: 0.400

Gnomad4 EAS AF: 0.119

Gnomad4 SAS AF: 0.306

Gnomad4 FIN AF: 0.453

Gnomad4 NFE AF: 0.424

Gnomad4 OTH AF: 0.364

Alfa AF: 0.408 Hom.: 6515

Bravo AF: 0.387

Asia WGS AF: 0.216 AC: 750 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	5.2
DANN	Benign	0.70

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs2270101; hg19: chr7-22936004;