Genetic Variant NM_006688.5:c.597+2866G>A (chr17-44964586-C-T) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

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

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.648

Publications

5 publications found

Variant links:

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]

C1QL1 links:

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]

NMT1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

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.

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	C1QL1	NM_006688.5	MANE Select	c.597+2866G>A		intron	N/A	NP_006679.1	O75973

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
C1QL1	ENST00000253407.4	TSL:1 MANE Select	c.597+2866G>A	intron	N/A	ENSP00000253407.2	O75973
NMT1	ENST00000678938.1		c.-110+6524C>T	intron	N/A	ENSP00000503621.1	P30419-2
C1QL1	ENST00000718438.1		c.687+2866G>A	intron	N/A	ENSP00000520823.1	A0ABB0MVI4

Frequencies

GnomAD3 genomes

AF:

0.629

AC:

95531

AN:

151880

Hom.:

31960

Cov.:

show subpopulations

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.:

AF XY:

0.623

AC XY:

46287

AN XY:

74294

show subpopulations

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

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.494

Heterozygous variant carriers

1595

3189

4784

6378

7973

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

758

1516

2274

3032

3790

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.576

Hom.:

67940

Bravo

AF:

0.637

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.89

CADD

Benign

0.81

(source)

DANN

Benign

0.29

PhyloP100

-0.65

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over