chr7-22954567-T-G

Variant names:

• chr7-22954567-T-G
• rs73082373
• NM_032581.4:c.991+5689A>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BS1 BS2

The NM_032581.4(HYCC1):​c.991+5689A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0242 in 151,566 control chromosomes in the GnomAD database, including 63 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 0.024 (63 hom., cov: 33)
• Consequence: HYCC1 NM_032581.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.210
• Publications: 4 publications found

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 Gene-Disease associations (from GenCC):

• hypomyelinating leukodystrophy 5

  Inheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Orphanet, Labcorp Genetics (formerly Invitae), G2P

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BS1: Variant frequency is greater than expected in population nfe. GnomAd4 allele frequency = 0.0242 (3672/151566) while in subpopulation NFE AF = 0.0348 (2349/67522). AF 95% confidence interval is 0.0336. There are 63 homozygotes in GnomAd4. There are 1814 alleles in the male GnomAd4 subpopulation. Median coverage is 33. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 63 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
HYCC1	NM_032581.4	c.991+5689A>C		intron_variant	Intron 10 of 10	ENST00000432176.7	NP_115970.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
HYCC1	ENST00000432176.7	c.991+5689A>C		intron_variant	Intron 10 of 10	1	NM_032581.4	ENSP00000403396.2

Frequencies

GnomAD3 genomes AF: 0.0243 AC: 3674 AN: 151442 Hom.: 63 Cov.: 33

Gnomad AFR AF: 0.00524

Gnomad AMI AF: 0.00440

Gnomad AMR AF: 0.0166

Gnomad ASJ AF: 0.0211

Gnomad EAS AF: 0.000385

Gnomad SAS AF: 0.0307

Gnomad FIN AF: 0.0540

Gnomad MID AF: 0.00735

Gnomad NFE AF: 0.0348

Gnomad OTH AF: 0.0261

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

GnomAD4 genome AF: 0.0242 AC: 3672 AN: 151566 Hom.: 63 Cov.: 33 AF XY: 0.0245 AC XY: 1814 AN XY: 74070

African (AFR) AF: 0.00523 AC: 217 AN: 41518

American (AMR) AF: 0.0167 AC: 254 AN: 15232

Ashkenazi Jewish (ASJ) AF: 0.0211 AC: 73 AN: 3460

East Asian (EAS) AF: 0.000386 AC: 2 AN: 5180

South Asian (SAS) AF: 0.0303 AC: 146 AN: 4818

European-Finnish (FIN) AF: 0.0540 AC: 571 AN: 10582

Middle Eastern (MID) AF: 0.00800 AC: 2 AN: 250

European-Non Finnish (NFE) AF: 0.0348 AC: 2349 AN: 67522

Other (OTH) AF: 0.0258 AC: 54 AN: 2094

Alfa AF: 0.0264 Hom.: 31

Bravo AF: 0.0194

Asia WGS AF: 0.0120 AC: 42 AN: 3428

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	5.9
DANN	Benign	0.83
PhyloP100		-0.21
Mutation Taster		=100/0	polymorphism

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

Other links and lift over

dbSNP: rs73082373; hg19: chr7-22994186;