rs2294693

Variant names:

• chr6-41037763-T-C
• rs2294693
• NM_173561.3:c.-62+1399A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_173561.3(UNC5CL):​c.-62+1399A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.262 in 152,188 control chromosomes in the GnomAD database, including 5,409 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 0.26 (5409 hom., cov: 33)
• Consequence: UNC5CL NM_173561.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.184
• Publications: 23 publications found

Genes affected

UNC5CL (HGNC:21203): (unc-5 family C-terminal like) Enables peptidase activity. Acts upstream of or within positive regulation of I-kappaB kinase/NF-kappaB signaling and positive regulation of JNK cascade. Located in membrane. [provided by Alliance of Genome Resources, Apr 2022]

OARD1 (HGNC:21257): (O-acyl-ADP-ribose deacylase 1) The protein encoded by this gene is a deacylase that can convert O-acetyl-ADP-ribose to ADP-ribose and acetate, O-propionyl-ADP-ribose to ADP-ribose and propionate, and O-butyryl-ADP-ribose to ADP-ribose and butyrate. The ADP-ribose product is able to inhibit these reactions through a competitive feedback loop. [provided by RefSeq, Jul 2016]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.321 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
UNC5CL	NM_173561.3	c.-62+1399A>G		intron_variant	Intron 1 of 8	ENST00000244565.8	NP_775832.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
UNC5CL	ENST00000244565.8	c.-62+1399A>G		intron_variant	Intron 1 of 8	1	NM_173561.3	ENSP00000244565.3
OARD1	ENST00000482853.5	n.*13-2628A>G		intron_variant	Intron 3 of 4	2		ENSP00000420472.1
UNC5CL	ENST00000714028.1	n.-62+1399A>G		intron_variant	Intron 1 of 7			ENSP00000519318.1

Frequencies

GnomAD3 genomes AF: 0.262 AC: 39887 AN: 152070 Hom.: 5407 Cov.: 33

Gnomad AFR AF: 0.323

Gnomad AMI AF: 0.247

Gnomad AMR AF: 0.277

Gnomad ASJ AF: 0.148

Gnomad EAS AF: 0.253

Gnomad SAS AF: 0.334

Gnomad FIN AF: 0.242

Gnomad MID AF: 0.158

Gnomad NFE AF: 0.228

Gnomad OTH AF: 0.226

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

GnomAD4 genome AF: 0.262 AC: 39908 AN: 152188 Hom.: 5409 Cov.: 33 AF XY: 0.263 AC XY: 19556 AN XY: 74402

African (AFR) AF: 0.323 AC: 13391 AN: 41520

American (AMR) AF: 0.277 AC: 4244 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.148 AC: 515 AN: 3470

East Asian (EAS) AF: 0.253 AC: 1311 AN: 5180

South Asian (SAS) AF: 0.335 AC: 1615 AN: 4822

European-Finnish (FIN) AF: 0.242 AC: 2561 AN: 10590

Middle Eastern (MID) AF: 0.160 AC: 47 AN: 294

European-Non Finnish (NFE) AF: 0.228 AC: 15526 AN: 67998

Other (OTH) AF: 0.224 AC: 473 AN: 2108

Alfa AF: 0.240 Hom.: 2392

Bravo AF: 0.264

Asia WGS AF: 0.322 AC: 1118 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	3.9
DANN	Benign	0.58
PhyloP100		-0.18
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: rs2294693; hg19: chr6-41005502;