1-11287435-C-G

Variant names:

• chr1-11287435-C-G
• rs17036631
• NM_013319.3:c.*1304C>G

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_013319.3(UBIAD1):​c.*1304C>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 0.00000658 in 152,086 control chromosomes in the GnomAD database, with no homozygous occurrence. 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 0.0000066 (0 hom., cov: 32)
• Consequence: UBIAD1 NM_013319.3 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.504
• Publications: 5 publications found

Genes affected

UBIAD1 (HGNC:30791): (UbiA prenyltransferase domain containing 1) This gene encodes a protein thought to be involved in cholesterol and phospholipid metabolism. Mutations in this gene are associated with Schnyder crystalline corneal dystrophy. [provided by RefSeq, Oct 2008]

UBIAD1 Gene-Disease associations (from GenCC):

• Schnyder corneal dystrophy

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

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
UBIAD1	NM_013319.3	c.*1304C>G		3_prime_UTR_variant	Exon 2 of 2	ENST00000376810.6	NP_037451.1
UBIAD1	NM_001330349.2	c.618+1703C>G		intron_variant	Intron 2 of 2		NP_001317278.1
UBIAD1	NM_001330350.2	c.530-7438C>G		intron_variant	Intron 1 of 1		NP_001317279.1
UBIAD1	XM_047418727.1	c.618+1703C>G		intron_variant	Intron 2 of 2		XP_047274683.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
UBIAD1	ENST00000376810.6	c.*1304C>G		3_prime_UTR_variant	Exon 2 of 2	1	NM_013319.3	ENSP00000366006.5
UBIAD1	ENST00000376804.2	c.530-7438C>G		intron_variant	Intron 1 of 1	2		ENSP00000366000.1
UBIAD1	ENST00000483738.1	c.216+1703C>G		intron_variant	Intron 2 of 2	3		ENSP00000473453.1
UBIAD1	ENST00000486588.6	n.261+1703C>G		intron_variant	Intron 2 of 4	5		ENSP00000473612.1

Frequencies

GnomAD3 genomes AF: 0.00000658 AC: 1 AN: 152086 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000655

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD4 exome Cov.: 0

GnomAD4 genome AF: 0.00000658 AC: 1 AN: 152086 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 74288

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00 AC: 0 AN: 41382

American (AMR) AF: 0.0000655 AC: 1 AN: 15264

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5188

South Asian (SAS) AF: 0.00 AC: 0 AN: 4830

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10592

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 68042

Other (OTH) AF: 0.00 AC: 0 AN: 2092

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5. (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

Alfa AF: 0.00 Hom.: 272

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	6.3
DANN	Benign	0.72
PhyloP100		-0.50

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: rs17036631; hg19: chr1-11347492;