17-44959823-G-C

Variant names:

• chr17-44959823-G-C
• rs1055646
• NM_006688.5:c.*365C>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.*365C>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.573 in 200,846 control chromosomes in the GnomAD database, including 34,845 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 0.59 (28255 hom., cov: 34)
  • Exomes 𝑓: 0.51 (6590 hom.)
• Consequence: C1QL1 NM_006688.5 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0600
• Publications: 3 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=-0.86).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.802 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
C1QL1	NM_006688.5	c.*365C>G		3_prime_UTR_variant	Exon 2 of 2	ENST00000253407.4	NP_006679.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
C1QL1	ENST00000253407.4	c.*365C>G		3_prime_UTR_variant	Exon 2 of 2	1	NM_006688.5	ENSP00000253407.2
C1QL1	ENST00000718438.1	c.*365C>G		3_prime_UTR_variant	Exon 2 of 2			ENSP00000520823.1
NMT1	ENST00000678938.1	c.-110+1761G>C		intron_variant	Intron 1 of 11			ENSP00000503621.1

Frequencies

GnomAD3 genomes AF: 0.592 AC: 90031 AN: 152078 Hom.: 28210 Cov.: 34

Gnomad AFR AF: 0.809

Gnomad AMI AF: 0.387

Gnomad AMR AF: 0.485

Gnomad ASJ AF: 0.512

Gnomad EAS AF: 0.449

Gnomad SAS AF: 0.550

Gnomad FIN AF: 0.468

Gnomad MID AF: 0.576

Gnomad NFE AF: 0.525

Gnomad OTH AF: 0.562

GnomAD4 exome AF: 0.511 AC: 24877 AN: 48652 Hom.: 6590 Cov.: 0 AF XY: 0.513 AC XY: 12408 AN XY: 24208

African (AFR) AF: 0.795 AC: 771 AN: 970

American (AMR) AF: 0.451 AC: 605 AN: 1342

Ashkenazi Jewish (ASJ) AF: 0.516 AC: 823 AN: 1596

East Asian (EAS) AF: 0.429 AC: 1065 AN: 2484

South Asian (SAS) AF: 0.531 AC: 1883 AN: 3544

European-Finnish (FIN) AF: 0.455 AC: 1008 AN: 2216

Middle Eastern (MID) AF: 0.626 AC: 159 AN: 254

European-Non Finnish (NFE) AF: 0.513 AC: 16923 AN: 32994

Other (OTH) AF: 0.504 AC: 1640 AN: 3252

GnomAD4 genome AF: 0.592 AC: 90126 AN: 152194 Hom.: 28255 Cov.: 34 AF XY: 0.585 AC XY: 43500 AN XY: 74410

African (AFR) AF: 0.810 AC: 33642 AN: 41552

American (AMR) AF: 0.485 AC: 7420 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.512 AC: 1777 AN: 3472

East Asian (EAS) AF: 0.449 AC: 2317 AN: 5156

South Asian (SAS) AF: 0.548 AC: 2641 AN: 4820

European-Finnish (FIN) AF: 0.468 AC: 4965 AN: 10606

Middle Eastern (MID) AF: 0.582 AC: 171 AN: 294

European-Non Finnish (NFE) AF: 0.525 AC: 35664 AN: 67978

Other (OTH) AF: 0.557 AC: 1176 AN: 2110

Alfa AF: 0.582 Hom.: 3314

Bravo AF: 0.601

Asia WGS AF: 0.514 AC: 1789 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	1.2
DANN	Benign	0.37
PhyloP100		0.060
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs1055646; hg19: chr17-43037191;