chr17-44962230-T-C

Position:

• chr17-44962230-T-C

Variant summary

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

The NM_006688.5(C1QL1):​c.598-1863A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.194 in 152,076 control chromosomes in the GnomAD database, including 3,764 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 0.19 (3764 hom., cov: 32)
• Consequence: C1QL1 NM_006688.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.439

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=-0.67).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.369 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
C1QL1	NM_006688.5	c.598-1863A>G		intron_variant		ENST00000253407.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
C1QL1	ENST00000253407.4	c.598-1863A>G		intron_variant		1	NM_006688.5	P1
NMT1	ENST00000678938.1	c.-110+4168T>C		intron_variant

Frequencies

GnomAD3 genomes AF: 0.194 AC: 29530 AN: 151958 Hom.: 3757 Cov.: 32

Gnomad AFR AF: 0.374

Gnomad AMI AF: 0.0242

Gnomad AMR AF: 0.130

Gnomad ASJ AF: 0.148

Gnomad EAS AF: 0.217

Gnomad SAS AF: 0.154

Gnomad FIN AF: 0.142

Gnomad MID AF: 0.228

Gnomad NFE AF: 0.114

Gnomad OTH AF: 0.181

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

GnomAD4 genome AF: 0.194 AC: 29576 AN: 152076 Hom.: 3764 Cov.: 32 AF XY: 0.195 AC XY: 14506 AN XY: 74358

Gnomad4 AFR AF: 0.374

Gnomad4 AMR AF: 0.130

Gnomad4 ASJ AF: 0.148

Gnomad4 EAS AF: 0.217

Gnomad4 SAS AF: 0.153

Gnomad4 FIN AF: 0.142

Gnomad4 NFE AF: 0.114

Gnomad4 OTH AF: 0.179

Alfa AF: 0.146 Hom.: 544

Bravo AF: 0.203

Asia WGS AF: 0.198 AC: 690 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.67
CADD	Benign	13
DANN	Benign	0.88

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.090		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: rs3024295; hg19: chr17-43039598;