6-41030094-G-T

Position:

• chr6-41030094-G-T

Variant summary

Our verdict is Benign. Variant got -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

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]

UNC5CL (HGNC:):

ACMG classification

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
UNC5CL	NM_173561.3	c.1334+294C>A		intron_variant		ENST00000244565.8	NP_775832.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
UNC5CL	ENST00000244565.8	c.1334+294C>A		intron_variant		1	NM_173561.3	ENSP00000244565.3
UNC5CL	ENST00000373164.1	c.1334+294C>A		intron_variant		1		ENSP00000362258.1
UNC5CL	ENST00000470102.1	n.421+294C>A		intron_variant		5

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

Gnomad4 AFR AF: 0.765

Gnomad4 AMR AF: 0.459

Gnomad4 ASJ AF: 0.368

Gnomad4 EAS AF: 0.404

Gnomad4 SAS AF: 0.488

Gnomad4 FIN AF: 0.405

Gnomad4 NFE AF: 0.371

Gnomad4 OTH AF: 0.462

Alfa AF: 0.395 Hom.: 7851

Bravo AF: 0.507

Asia WGS AF: 0.512 AC: 1779 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	0.76
DANN	Benign	0.42

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

Publications

LitVar

Other links and lift over

dbSNP: rs736794; hg19: chr6-40997833;