dbSNP rs7788668: HYCC1:c.*4570G>T (chr7-22941019-C-A) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_032581.4(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
NM_032581.4 3_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.217

Publications

5 publications found

Variant links:

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

HYCC1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
HYCC1	NM_032581.4 link	c.*4570G>T		3_prime_UTR_variant	Exon 11 of 11	ENST00000432176.7	NP_115970.2	Q9BYI3-1

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein	UniProt
HYCC1	ENST00000432176.7 link	c.*4570G>T	3_prime_UTR_variant	Exon 11 of 11	1	NM_032581.4	ENSP00000403396.2	Q9BYI3-1
HYCC1	ENST00000421730.1 link	n.90G>T	non_coding_transcript_exon_variant	Exon 2 of 4	4
HYCC1	ENST00000465661.2 link	n.1182+19237G>T	intron_variant	Intron 10 of 10	3
HYCC1	ENST00000440481.6 link	c.*5172G>T	downstream_gene_variant		1		ENSP00000397168.2	H7C0W7

Frequencies

GnomAD3 genomes

AF:

0.276

AC:

41847

AN:

151762

Hom.:

5976

Cov.:

show subpopulations

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:

AN:

Hom.:

Cov.:

AF XY:

0.200

AC XY:

AN XY:

show subpopulations

African (AFR)

AC:

AN:

American (AMR)

AF:

0.00

AC:

AN:

Ashkenazi Jewish (ASJ)

AC:

AN:

East Asian (EAS)

AC:

AN:

South Asian (SAS)

AF:

0.00

AC:

AN:

European-Finnish (FIN)

AF:

0.500

AC:

AN:

Middle Eastern (MID)

AC:

AN:

European-Non Finnish (NFE)

AF:

0.375

AC:

AN:

Other (OTH)

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.575

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.276

AC:

41873

AN:

151880

Hom.:

5978

Cov.:

AF XY:

0.277

AC XY:

20559

AN XY:

74228

show subpopulations

African (AFR)

AF:

0.205

AC:

8503

AN:

41412

American (AMR)

AF:

0.310

AC:

4721

AN:

15246

Ashkenazi Jewish (ASJ)

AF:

0.263

AC:

913

AN:

3466

East Asian (EAS)

AF:

0.101

AC:

523

AN:

5164

South Asian (SAS)

AF:

0.269

AC:

1294

AN:

4810

European-Finnish (FIN)

AF:

0.315

AC:

3312

AN:

10530

Middle Eastern (MID)

AF:

0.312

AC:

AN:

292

European-Non Finnish (NFE)

AF:

0.319

AC:

21701

AN:

67936

Other (OTH)

AF:

0.261

AC:

552

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

1486

2972

4458

5944

7430

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

442

884

1326

1768

2210

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.298

Hom.:

29778

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

(source)

DANN

Benign

0.56

PhyloP100

-0.22

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over