17-44962230-T-C

Variant names:

• chr17-44962230-T-C
• rs3024295
• NM_006688.5:c.598-1863A>G

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 2 publications found

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

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_006688.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	C1QL1	NM_006688.5	MANE Select	c.598-1863A>G		intron	N/A	NP_006679.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	C1QL1	ENST00000253407.4	TSL:1 MANE Select	c.598-1863A>G		intron	N/A	ENSP00000253407.2
	NMT1	ENST00000678938.1		c.-110+4168T>C		intron	N/A	ENSP00000503621.1
	C1QL1	ENST00000718438.1		c.688-1863A>G		intron	N/A	ENSP00000520823.1

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

African (AFR) AF: 0.374 AC: 15487 AN: 41450

American (AMR) AF: 0.130 AC: 1991 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.148 AC: 512 AN: 3468

East Asian (EAS) AF: 0.217 AC: 1125 AN: 5176

South Asian (SAS) AF: 0.153 AC: 740 AN: 4826

European-Finnish (FIN) AF: 0.142 AC: 1505 AN: 10594

Middle Eastern (MID) AF: 0.221 AC: 65 AN: 294

European-Non Finnish (NFE) AF: 0.114 AC: 7750 AN: 67974

Other (OTH) AF: 0.179 AC: 379 AN: 2112

Alfa AF: 0.140 Hom.: 652

Bravo AF: 0.203

Asia WGS AF: 0.198 AC: 690 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.67
CADD	Benign	13
DANN	Benign	0.88
PhyloP100		-0.44
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs3024295; hg19: chr17-43039598;