rs886045057

Variant names:

• chr1-11273221-C-T
• rs886045057
• NM_013319.3:c.-311C>T

Variant summary

Our verdict is Benign. The variant received -9 ACMG points: 0P and 9B. BP4_Strong BS1_Supporting BS2

The NM_013319.3(UBIAD1):​c.-311C>T variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000251 in 362,042 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000073 (0 hom., cov: 30)
  • Exomes 𝑓: 0.00038 (1 hom.)
• Consequence: UBIAD1 NM_013319.3 5_prime_UTR
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.420
• Publications: 0 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: Ambry Genetics, G2P, Labcorp Genetics (formerly Invitae), Orphanet

ACMG classification

Our verdict: Benign. The variant received -9 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.53).
• BS1: Variant frequency is greater than expected in population sas. GnomAd4 allele frequency = 0.0000729 (11/150912) while in subpopulation SAS AF = 0.00126 (6/4750). AF 95% confidence interval is 0.000549. There are 0 homozygotes in GnomAd4. There are 8 alleles in the male GnomAd4 subpopulation. Median coverage is 30. This position passed quality control check. Existence of Clinvar submissions makes me limit the strength of this signal to Supporting
• BS2: High AC in GnomAd4 at 11 AD gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_013319.3. 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
	UBIAD1	NM_013319.3	MANE Select	c.-311C>T		5_prime_UTR	Exon 1 of 2	NP_037451.1	Q9Y5Z9-1
	UBIAD1	NM_001330349.2		c.-311C>T		5_prime_UTR	Exon 1 of 3	NP_001317278.1
	UBIAD1	NM_001330350.2		c.-311C>T		5_prime_UTR	Exon 1 of 2	NP_001317279.1	Q9Y5Z9-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	UBIAD1	ENST00000376810.6	TSL:1 MANE Select	c.-311C>T		5_prime_UTR	Exon 1 of 2	ENSP00000366006.5	Q9Y5Z9-1

Frequencies

GnomAD3 genomes AF: 0.0000729 AC: 11 AN: 150912 Hom.: 0 Cov.: 30

Gnomad AFR AF: 0.0000732

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000659

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00126

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000148

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.000379 AC: 80 AN: 211130 Hom.: 1 Cov.: 0 AF XY: 0.000495 AC XY: 56 AN XY: 113238

African (AFR) AF: 0.00 AC: 0 AN: 4848

American (AMR) AF: 0.00 AC: 0 AN: 7400

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 5754

East Asian (EAS) AF: 0.00 AC: 0 AN: 9742

South Asian (SAS) AF: 0.00207 AC: 70 AN: 33808

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 11346

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 818

European-Non Finnish (NFE) AF: 0.0000477 AC: 6 AN: 125894

Other (OTH) AF: 0.000347 AC: 4 AN: 11520

GnomAD4 genome AF: 0.0000729 AC: 11 AN: 150912 Hom.: 0 Cov.: 30 AF XY: 0.000109 AC XY: 8 AN XY: 73624

African (AFR) AF: 0.0000732 AC: 3 AN: 41006

American (AMR) AF: 0.0000659 AC: 1 AN: 15174

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3468

East Asian (EAS) AF: 0.00 AC: 0 AN: 5120

South Asian (SAS) AF: 0.00126 AC: 6 AN: 4750

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10426

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

European-Non Finnish (NFE) AF: 0.0000148 AC: 1 AN: 67680

Other (OTH) AF: 0.00 AC: 0 AN: 2072

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.0000340

Asia WGS AF: 0.000289 AC: 1 AN: 3478

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	Schnyder crystalline corneal dystrophy (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.53
CADD	Benign	15
DANN	Uncertain	0.99
PhyloP100		-0.42
PromoterAI		0.014	Neutral
Mutation Taster		=299/1	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: rs886045057; hg19: chr1-11333278;