rs2286492

Variant names:

• chr7-22945391-A-C
• rs2286492
• NM_032581.4:c.*198T>G

Your query was ambiguous. Multiple possible variants found:

• chr7-22945391-A-C
• chr7-22945391-A-G
• chr7-22945391-A-T

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_032581.4(HYCC1):​c.*198T>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0908 in 592,352 control chromosomes in the GnomAD database, including 2,648 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.075 (533 hom., cov: 32)
  • Exomes 𝑓: 0.096 (2115 hom.)
• Consequence: HYCC1 NM_032581.4 3_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.0580
• Publications: 14 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: Labcorp Genetics (formerly Invitae), ClinGen, G2P, Orphanet

ACMG classification

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BP6: Variant 7-22945391-A-C is Benign according to our data. Variant chr7-22945391-A-C is described in ClinVar as Benign. ClinVar VariationId is 359764.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.107 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_032581.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HYCC1	NM_032581.4	MANE Select	c.*198T>G		3_prime_UTR	Exon 11 of 11	NP_115970.2
	HYCC1	NM_001363466.2		c.*800T>G		3_prime_UTR	Exon 12 of 12	NP_001350395.1	Q9BYI3-3
	HYCC1	NM_001363467.2		c.*758T>G		3_prime_UTR	Exon 12 of 12	NP_001350396.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HYCC1	ENST00000432176.7	TSL:1 MANE Select	c.*198T>G		3_prime_UTR	Exon 11 of 11	ENSP00000403396.2	Q9BYI3-1
	HYCC1	ENST00000440481.6	TSL:1	c.*800T>G		3_prime_UTR	Exon 11 of 11	ENSP00000397168.2	H7C0W7
	HYCC1	ENST00000905181.1		c.*198T>G		3_prime_UTR	Exon 11 of 11	ENSP00000575240.1

Frequencies

GnomAD3 genomes AF: 0.0754 AC: 11470 AN: 152064 Hom.: 533 Cov.: 32

Gnomad AFR AF: 0.0171

Gnomad AMI AF: 0.0384

Gnomad AMR AF: 0.0677

Gnomad ASJ AF: 0.0980

Gnomad EAS AF: 0.115

Gnomad SAS AF: 0.101

Gnomad FIN AF: 0.111

Gnomad MID AF: 0.0981

Gnomad NFE AF: 0.101

Gnomad OTH AF: 0.0793

GnomAD4 exome AF: 0.0962 AC: 42341 AN: 440170 Hom.: 2115 Cov.: 3 AF XY: 0.0971 AC XY: 22563 AN XY: 232300

African (AFR) AF: 0.0136 AC: 164 AN: 12090

American (AMR) AF: 0.0571 AC: 1054 AN: 18444

Ashkenazi Jewish (ASJ) AF: 0.104 AC: 1409 AN: 13530

East Asian (EAS) AF: 0.116 AC: 3567 AN: 30770

South Asian (SAS) AF: 0.0967 AC: 4142 AN: 42840

European-Finnish (FIN) AF: 0.109 AC: 3161 AN: 28940

Middle Eastern (MID) AF: 0.0832 AC: 161 AN: 1934

European-Non Finnish (NFE) AF: 0.0994 AC: 26435 AN: 266026

Other (OTH) AF: 0.0878 AC: 2248 AN: 25596

GnomAD4 genome AF: 0.0753 AC: 11464 AN: 152182 Hom.: 533 Cov.: 32 AF XY: 0.0766 AC XY: 5700 AN XY: 74404

African (AFR) AF: 0.0170 AC: 707 AN: 41546

American (AMR) AF: 0.0676 AC: 1031 AN: 15258

Ashkenazi Jewish (ASJ) AF: 0.0980 AC: 340 AN: 3468

East Asian (EAS) AF: 0.115 AC: 593 AN: 5162

South Asian (SAS) AF: 0.101 AC: 488 AN: 4828

European-Finnish (FIN) AF: 0.111 AC: 1183 AN: 10628

Middle Eastern (MID) AF: 0.0952 AC: 28 AN: 294

European-Non Finnish (NFE) AF: 0.101 AC: 6894 AN: 67972

Other (OTH) AF: 0.0781 AC: 165 AN: 2114

Alfa AF: 0.0915 Hom.: 1629

Bravo AF: 0.0676

Asia WGS AF: 0.0920 AC: 319 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	1	Hypomyelination and Congenital Cataract (1)
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	1.1
DANN	Benign	0.68
PhyloP100		-0.058
Mutation Taster		=100/0	polymorphism (auto)

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: rs2286492; hg19: chr7-22985010;