rs11071021

chr15-54064094-G-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001080534.3(UNC13C):c.2983+48208G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.422 in 150,672 control chromosomes in the GnomAD database, including 16,435 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 0.42 (16435 hom., cov: 30)
• Consequence: UNC13C NM_001080534.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0380

Genes affected

UNC13C (HGNC:23149): (unc-13 homolog C) Predicted to enable calmodulin binding activity and syntaxin-1 binding activity. Predicted to be involved in several processes, including glutamatergic synaptic transmission; regulated exocytosis; and synaptic vesicle maturation. Predicted to be located in presynaptic active zone. Predicted to be active in several cellular components, including axon terminus; parallel fiber to Purkinje cell synapse; and presynaptic active zone cytoplasmic component. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.569 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
UNC13C	NM_001080534.3	c.2983+48208G>T		intron_variant		ENST00000260323.16

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
UNC13C	ENST00000260323.16	c.2983+48208G>T		intron_variant		5	NM_001080534.3	A1
UNC13C	ENST00000647821.1	c.2983+48208G>T		intron_variant				P4

Frequencies

GnomAD3 genomes AF: 0.423 AC: 63672 AN: 150554 Hom.: 16445 Cov.: 30

Gnomad AFR AF: 0.118

Gnomad AMI AF: 0.763

Gnomad AMR AF: 0.459

Gnomad ASJ AF: 0.592

Gnomad EAS AF: 0.344

Gnomad SAS AF: 0.334

Gnomad FIN AF: 0.566

Gnomad MID AF: 0.443

Gnomad NFE AF: 0.574

Gnomad OTH AF: 0.473

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

GnomAD4 genome AF: 0.422 AC: 63650 AN: 150672 Hom.: 16435 Cov.: 30 AF XY: 0.420 AC XY: 30892 AN XY: 73564

Gnomad4 AFR AF: 0.118

Gnomad4 AMR AF: 0.458

Gnomad4 ASJ AF: 0.592

Gnomad4 EAS AF: 0.344

Gnomad4 SAS AF: 0.334

Gnomad4 FIN AF: 0.566

Gnomad4 NFE AF: 0.574

Gnomad4 OTH AF: 0.470

Alfa AF: 0.527 Hom.: 12407

Bravo AF: 0.401

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
Cadd	Benign	1.6
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: rs11071021; hg19: chr15-54356291; COSMIC: COSV52872156;