rs1055646

Positions:

• chr17-44959823-G-C

Variant summary

Our verdict is Benign. Variant got -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

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=-0.86).
• 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/exons	MANE	Protein	UniProt
C1QL1	NM_006688.5	c.*365C>G		3_prime_UTR_variant	2/2	ENST00000253407.4	NP_006679.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
C1QL1	ENST00000253407	c.*365C>G		3_prime_UTR_variant	2/2	1	NM_006688.5	ENSP00000253407.2
NMT1	ENST00000678938.1	c.-110+1761G>C		intron_variant				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

Gnomad4 AFR exome AF: 0.795

Gnomad4 AMR exome AF: 0.451

Gnomad4 ASJ exome AF: 0.516

Gnomad4 EAS exome AF: 0.429

Gnomad4 SAS exome AF: 0.531

Gnomad4 FIN exome AF: 0.455

Gnomad4 NFE exome AF: 0.513

Gnomad4 OTH exome AF: 0.504

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

Gnomad4 AFR AF: 0.810

Gnomad4 AMR AF: 0.485

Gnomad4 ASJ AF: 0.512

Gnomad4 EAS AF: 0.449

Gnomad4 SAS AF: 0.548

Gnomad4 FIN AF: 0.468

Gnomad4 NFE AF: 0.525

Gnomad4 OTH AF: 0.557

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

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: rs1055646; hg19: chr17-43037191;