rs9394755

Variant names:

• chr6-41038941-T-C
• rs9394755
• NM_173561.3:c.-62+221A>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+221A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.252 in 152,058 control chromosomes in the GnomAD database, including 5,019 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 0.25 (5019 hom., cov: 32)
• Consequence: UNC5CL NM_173561.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.500
• Publications: 6 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=-0.93).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.315 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
UNC5CL	NM_173561.3	c.-62+221A>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+221A>G		intron_variant	Intron 1 of 8	1	NM_173561.3	ENSP00000244565.3
OARD1	ENST00000482853.5	n.*13-3806A>G		intron_variant	Intron 3 of 4	2		ENSP00000420472.1
UNC5CL	ENST00000714028.1	n.-62+221A>G		intron_variant	Intron 1 of 7			ENSP00000519318.1

Frequencies

GnomAD3 genomes AF: 0.252 AC: 38236 AN: 151940 Hom.: 5018 Cov.: 32

Gnomad AFR AF: 0.321

Gnomad AMI AF: 0.175

Gnomad AMR AF: 0.270

Gnomad ASJ AF: 0.139

Gnomad EAS AF: 0.252

Gnomad SAS AF: 0.309

Gnomad FIN AF: 0.232

Gnomad MID AF: 0.136

Gnomad NFE AF: 0.213

Gnomad OTH AF: 0.214

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

GnomAD4 genome AF: 0.252 AC: 38256 AN: 152058 Hom.: 5019 Cov.: 32 AF XY: 0.252 AC XY: 18739 AN XY: 74300

African (AFR) AF: 0.320 AC: 13265 AN: 41450

American (AMR) AF: 0.270 AC: 4131 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.139 AC: 481 AN: 3470

East Asian (EAS) AF: 0.252 AC: 1301 AN: 5164

South Asian (SAS) AF: 0.310 AC: 1492 AN: 4820

European-Finnish (FIN) AF: 0.232 AC: 2461 AN: 10586

Middle Eastern (MID) AF: 0.136 AC: 40 AN: 294

European-Non Finnish (NFE) AF: 0.213 AC: 14476 AN: 67974

Other (OTH) AF: 0.213 AC: 449 AN: 2112

Alfa AF: 0.244 Hom.: 841

Bravo AF: 0.254

Asia WGS AF: 0.316 AC: 1098 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	1.6
DANN	Benign	0.41
PhyloP100		-0.50
PromoterAI		0.016	Neutral
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: rs9394755; hg19: chr6-41006680;