rs7168338

Positions:

• chr15-70687977-T-C
• chr15-70687977-T-G

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BA1

The NM_018003.4(UACA):​c.425-157A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.129 in 152,178 control chromosomes in the GnomAD database, including 1,488 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 0.13 (1488 hom., cov: 32)
• Consequence: UACA NM_018003.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.588

Genes affected

UACA (HGNC:15947): (uveal autoantigen with coiled-coil domains and ankyrin repeats) This gene encodes a protein that contains ankyrin repeats and coiled coil domains and likely plays a role in apoptosis. Studies in rodents have implicated the encoded protein in the stimulation of apoptosis and the regulation of mammary gland involution, in which the mammary gland returns to its pre-pregnant state. This protein has also been proposed to negatively regulate apoptosis based on experiments in human cell lines in which the protein was shown to interact with PRKC apoptosis WT1 regulator protein, also known as PAR-4, and inhibit translocation of the PAR-4 receptor. Autoantibodies to this protein have been identified in human patients with panuveitis and Graves' disease. Differential expression of this gene has been observed in various human cancers. [provided by RefSeq, May 2017]

ACMG classification

Verdict is Benign. Variant got -8 ACMG points.

• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.201 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
UACA	NM_018003.4	c.425-157A>G		intron_variant		ENST00000322954.11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
UACA	ENST00000322954.11	c.425-157A>G		intron_variant		1	NM_018003.4	P1

Frequencies

GnomAD3 genomes AF: 0.129 AC: 19663 AN: 152060 Hom.: 1486 Cov.: 32

Gnomad AFR AF: 0.205

Gnomad AMI AF: 0.0461

Gnomad AMR AF: 0.0933

Gnomad ASJ AF: 0.132

Gnomad EAS AF: 0.0799

Gnomad SAS AF: 0.145

Gnomad FIN AF: 0.111

Gnomad MID AF: 0.120

Gnomad NFE AF: 0.0983

Gnomad OTH AF: 0.116

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.129 AC: 19675 AN: 152178 Hom.: 1488 Cov.: 32 AF XY: 0.127 AC XY: 9475 AN XY: 74392

Gnomad4 AFR AF: 0.205

Gnomad4 AMR AF: 0.0932

Gnomad4 ASJ AF: 0.132

Gnomad4 EAS AF: 0.0797

Gnomad4 SAS AF: 0.144

Gnomad4 FIN AF: 0.111

Gnomad4 NFE AF: 0.0983

Gnomad4 OTH AF: 0.114

Alfa AF: 0.0939 Hom.: 368

Bravo AF: 0.131

Asia WGS AF: 0.111 AC: 388 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
CADD	Benign	19
DANN	Benign	0.78

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.21		Details are displayed if max score is > 0.2
DS_AG_spliceai		0.21		Position offset: 0

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs7168338; hg19: chr15-70980316;