6-41030094-G-T

Variant names:

• chr6-41030094-G-T
• rs736794
• NM_173561.3:c.1334+294C>A

Variant summary

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

The NM_173561.3(UNC5CL):​c.1334+294C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.495 in 152,032 control chromosomes in the GnomAD database, including 20,930 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 0.50 (20930 hom., cov: 32)
• Consequence: UNC5CL NM_173561.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.155
• Publications: 5 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]

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.94).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.758 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_173561.3. 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
	UNC5CL	NM_173561.3	MANE Select	c.1334+294C>A		intron	N/A	NP_775832.2	Q8IV45

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	UNC5CL	ENST00000244565.8	TSL:1 MANE Select	c.1334+294C>A		intron	N/A	ENSP00000244565.3	Q8IV45
	UNC5CL	ENST00000373164.1	TSL:1	c.1334+294C>A		intron	N/A	ENSP00000362258.1	Q8IV45
	UNC5CL	ENST00000470102.1	TSL:5	n.421+294C>A		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.495 AC: 75217 AN: 151914 Hom.: 20879 Cov.: 32

Gnomad AFR AF: 0.765

Gnomad AMI AF: 0.258

Gnomad AMR AF: 0.459

Gnomad ASJ AF: 0.368

Gnomad EAS AF: 0.405

Gnomad SAS AF: 0.489

Gnomad FIN AF: 0.405

Gnomad MID AF: 0.404

Gnomad NFE AF: 0.371

Gnomad OTH AF: 0.465

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

GnomAD4 genome AF: 0.495 AC: 75320 AN: 152032 Hom.: 20930 Cov.: 32 AF XY: 0.495 AC XY: 36778 AN XY: 74322

African (AFR) AF: 0.765 AC: 31745 AN: 41484

American (AMR) AF: 0.459 AC: 7018 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.368 AC: 1279 AN: 3472

East Asian (EAS) AF: 0.404 AC: 2090 AN: 5168

South Asian (SAS) AF: 0.488 AC: 2347 AN: 4806

European-Finnish (FIN) AF: 0.405 AC: 4265 AN: 10540

Middle Eastern (MID) AF: 0.408 AC: 119 AN: 292

European-Non Finnish (NFE) AF: 0.371 AC: 25246 AN: 67972

Other (OTH) AF: 0.462 AC: 976 AN: 2112

Alfa AF: 0.396 Hom.: 12728

Bravo AF: 0.507

Asia WGS AF: 0.512 AC: 1779 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	0.76
DANN	Benign	0.42
PhyloP100		-0.15
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: rs736794; hg19: chr6-40997833;