rs3024293

Positions:

• chr17-44962350-T-A
• chr17-44962350-T-G

Variant summary

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

The NM_006688.5(C1QL1):​c.598-1983A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.314 in 152,090 control chromosomes in the GnomAD database, including 8,264 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 0.31 (8264 hom., cov: 32)
• Consequence: C1QL1 NM_006688.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0240

Genes affected

C1QL1 (HGNC:24182): (complement C1q like 1) Predicted to enable signaling receptor binding activity. Predicted to act upstream of or within maintenance of synapse structure; motor learning; and neuron remodeling. Predicted to be located in several cellular components, including climbing fiber; presynapse; and synaptic cleft. Predicted to be part of collagen trimer. [provided by Alliance of Genome Resources, Apr 2022]

NMT1 (HGNC:7857): (N-myristoyltransferase 1) Myristate, a rare 14-carbon saturated fatty acid, is cotranslationally attached by an amide linkage to the N-terminal glycine residue of cellular and viral proteins with diverse functions. N-myristoyltransferase (NMT; EC 2.3.1.97) catalyzes the transfer of myristate from CoA to proteins. N-myristoylation appears to be irreversible and is required for full expression of the biologic activities of several N-myristoylated proteins, including the alpha subunit of the signal-transducing guanine nucleotide-binding protein (G protein) GO (GNAO1; MIM 139311) (Duronio et al., 1992 [PubMed 1570339]).[supplied by OMIM, Nov 2008]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.455 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
C1QL1	NM_006688.5	c.598-1983A>T		intron_variant		ENST00000253407.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
C1QL1	ENST00000253407.4	c.598-1983A>T		intron_variant		1	NM_006688.5	P1
NMT1	ENST00000678938.1	c.-110+4288T>A		intron_variant

Frequencies

GnomAD3 genomes AF: 0.314 AC: 47716 AN: 151972 Hom.: 8247 Cov.: 32

Gnomad AFR AF: 0.449

Gnomad AMI AF: 0.164

Gnomad AMR AF: 0.273

Gnomad ASJ AF: 0.248

Gnomad EAS AF: 0.470

Gnomad SAS AF: 0.260

Gnomad FIN AF: 0.325

Gnomad MID AF: 0.358

Gnomad NFE AF: 0.237

Gnomad OTH AF: 0.309

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

GnomAD4 genome AF: 0.314 AC: 47777 AN: 152090 Hom.: 8264 Cov.: 32 AF XY: 0.318 AC XY: 23607 AN XY: 74342

Gnomad4 AFR AF: 0.449

Gnomad4 AMR AF: 0.274

Gnomad4 ASJ AF: 0.248

Gnomad4 EAS AF: 0.471

Gnomad4 SAS AF: 0.259

Gnomad4 FIN AF: 0.325

Gnomad4 NFE AF: 0.237

Gnomad4 OTH AF: 0.309

Alfa AF: 0.278 Hom.: 855

Bravo AF: 0.319

Asia WGS AF: 0.346 AC: 1201 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	4.7
DANN	Benign	0.81

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: rs3024293; hg19: chr17-43039718;