rs2981586

Variant names:

• chr17-44964586-C-T
• rs2981586
• NM_006688.5:c.597+2866G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_006688.5(C1QL1):​c.597+2866G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.629 in 151,998 control chromosomes in the GnomAD database, including 32,016 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 0.63 (32016 hom., cov: 32)
• Consequence: C1QL1 NM_006688.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.648
• Publications: 5 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=-0.89).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.869 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
C1QL1	NM_006688.5	c.597+2866G>A		intron_variant	Intron 1 of 1	ENST00000253407.4	NP_006679.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
C1QL1	ENST00000253407.4	c.597+2866G>A		intron_variant	Intron 1 of 1	1	NM_006688.5	ENSP00000253407.2
NMT1	ENST00000678938.1	c.-110+6524C>T		intron_variant	Intron 1 of 11			ENSP00000503621.1
C1QL1	ENST00000718438.1	c.687+2866G>A		intron_variant	Intron 1 of 1			ENSP00000520823.1

Frequencies

GnomAD3 genomes AF: 0.629 AC: 95531 AN: 151880 Hom.: 31960 Cov.: 32

Gnomad AFR AF: 0.876

Gnomad AMI AF: 0.386

Gnomad AMR AF: 0.505

Gnomad ASJ AF: 0.518

Gnomad EAS AF: 0.510

Gnomad SAS AF: 0.566

Gnomad FIN AF: 0.524

Gnomad MID AF: 0.595

Gnomad NFE AF: 0.546

Gnomad OTH AF: 0.594

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

GnomAD4 genome AF: 0.629 AC: 95637 AN: 151998 Hom.: 32016 Cov.: 32 AF XY: 0.623 AC XY: 46287 AN XY: 74294

African (AFR) AF: 0.876 AC: 36357 AN: 41496

American (AMR) AF: 0.505 AC: 7725 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.518 AC: 1795 AN: 3468

East Asian (EAS) AF: 0.511 AC: 2621 AN: 5132

South Asian (SAS) AF: 0.564 AC: 2716 AN: 4816

European-Finnish (FIN) AF: 0.524 AC: 5532 AN: 10550

Middle Eastern (MID) AF: 0.602 AC: 177 AN: 294

European-Non Finnish (NFE) AF: 0.546 AC: 37120 AN: 67938

Other (OTH) AF: 0.590 AC: 1244 AN: 2110

Alfa AF: 0.576 Hom.: 67940

Bravo AF: 0.637

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.81
DANN	Benign	0.29
PhyloP100		-0.65
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: rs2981586; hg19: chr17-43041954;