1-11287435-C-T

Variant names:

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

Variant summary

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

The NM_013319.3(UBIAD1):​c.*1304C>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 0.0948 in 152,180 control chromosomes in the GnomAD database, including 1,126 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.095 (1126 hom., cov: 32)
  • Exomes 𝑓: 0.10 (0 hom.)
• Consequence: UBIAD1 NM_013319.3 3_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• 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: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.8).
• BP6: Variant 1-11287435-C-T is Benign according to our data. Variant chr1-11287435-C-T is described in ClinVar as Benign. ClinVar VariationId is 291894.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.205 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
UBIAD1	NM_013319.3	c.*1304C>T		3_prime_UTR_variant	Exon 2 of 2	ENST00000376810.6	NP_037451.1
UBIAD1	NM_001330349.2	c.618+1703C>T		intron_variant	Intron 2 of 2		NP_001317278.1
UBIAD1	NM_001330350.2	c.530-7438C>T		intron_variant	Intron 1 of 1		NP_001317279.1
UBIAD1	XM_047418727.1	c.618+1703C>T		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>T		3_prime_UTR_variant	Exon 2 of 2	1	NM_013319.3	ENSP00000366006.5
UBIAD1	ENST00000376804.2	c.530-7438C>T		intron_variant	Intron 1 of 1	2		ENSP00000366000.1
UBIAD1	ENST00000483738.1	c.216+1703C>T		intron_variant	Intron 2 of 2	3		ENSP00000473453.1
UBIAD1	ENST00000486588.6	n.261+1703C>T		intron_variant	Intron 2 of 4	5		ENSP00000473612.1

Frequencies

GnomAD3 genomes AF: 0.0947 AC: 14405 AN: 152052 Hom.: 1126 Cov.: 32

Gnomad AFR AF: 0.209

Gnomad AMI AF: 0.00220

Gnomad AMR AF: 0.0461

Gnomad ASJ AF: 0.0545

Gnomad EAS AF: 0.115

Gnomad SAS AF: 0.135

Gnomad FIN AF: 0.0557

Gnomad MID AF: 0.0411

Gnomad NFE AF: 0.0418

Gnomad OTH AF: 0.0865

GnomAD4 exome AF: 0.100 AC: 1 AN: 10 Hom.: 0 Cov.: 0 AF XY: 0.250 AC XY: 1 AN XY: 4

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 4

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 4

Other (OTH) AF: 0.500 AC: 1 AN: 2

GnomAD4 genome AF: 0.0948 AC: 14433 AN: 152170 Hom.: 1126 Cov.: 32 AF XY: 0.0951 AC XY: 7079 AN XY: 74400

African (AFR) AF: 0.209 AC: 8661 AN: 41484

American (AMR) AF: 0.0459 AC: 702 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.0545 AC: 189 AN: 3468

East Asian (EAS) AF: 0.116 AC: 598 AN: 5174

South Asian (SAS) AF: 0.134 AC: 649 AN: 4826

European-Finnish (FIN) AF: 0.0557 AC: 590 AN: 10590

Middle Eastern (MID) AF: 0.0442 AC: 13 AN: 294

European-Non Finnish (NFE) AF: 0.0418 AC: 2846 AN: 68028

Other (OTH) AF: 0.0866 AC: 183 AN: 2114

Alfa AF: 0.0553 Hom.: 272

Bravo AF: 0.0955

Asia WGS AF: 0.135 AC: 467 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:1

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Schnyder crystalline corneal dystrophy Benign:1

Jan 13, 2018

Illumina Laboratory Services, Illumina

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	5.9
DANN	Benign	0.81
PhyloP100		-0.50
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: rs17036631; hg19: chr1-11347492;