rs7909832

Variant names:

• chr10-16514711-T-C
• rs7909832
• NM_001010908.2:c.589-4A>G

Variant summary

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

The NM_001010908.2(C1QL3):​c.589-4A>G variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.563 in 1,601,128 control chromosomes in the GnomAD database, including 256,415 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.57 (25386 hom., cov: 33)
  • Exomes 𝑓: 0.56 (231029 hom.)
• Consequence: C1QL3 NM_001010908.2 splice_region, intron
• Scores: Splicing: ADA: 0.0001523
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.79
• Publications: 50 publications found

Genes affected

C1QL3 (HGNC:19359): (complement C1q like 3) Predicted to enable identical protein binding activity. Predicted to act upstream of or within regulation of synapse organization. Predicted to be located in extracellular region. Predicted to be part of collagen trimer. [provided by Alliance of Genome Resources, Apr 2022]

PTER (HGNC:9590): (phosphotriesterase related) Predicted to enable hydrolase activity, acting on ester bonds and zinc ion binding activity. Involved in epithelial cell differentiation. Located in extracellular exosome. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.658 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
C1QL3	NM_001010908.2	c.589-4A>G		splice_region_variant, intron_variant	Intron 1 of 1	ENST00000298943.4	NP_001010908.1
PTER	XR_007062017.1	n.2492-2005T>C		intron_variant	Intron 6 of 6
PTER	XR_007062018.1	n.2103-2005T>C		intron_variant	Intron 5 of 5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
C1QL3	ENST00000298943.4	c.589-4A>G		splice_region_variant, intron_variant	Intron 1 of 1	1	NM_001010908.2	ENSP00000298943.3
C1QL3	ENST00000718439.1	c.685-4A>G		splice_region_variant, intron_variant	Intron 1 of 1			ENSP00000520824.1

Frequencies

GnomAD3 genomes AF: 0.574 AC: 87140 AN: 151928 Hom.: 25370 Cov.: 33

Gnomad AFR AF: 0.664

Gnomad AMI AF: 0.576

Gnomad AMR AF: 0.562

Gnomad ASJ AF: 0.509

Gnomad EAS AF: 0.508

Gnomad SAS AF: 0.587

Gnomad FIN AF: 0.364

Gnomad MID AF: 0.703

Gnomad NFE AF: 0.560

Gnomad OTH AF: 0.591

GnomAD2 exomes AF: 0.556 AC: 134854 AN: 242592 AF XY: 0.557

Gnomad AFR exome AF: 0.671

Gnomad AMR exome AF: 0.599

Gnomad ASJ exome AF: 0.519

Gnomad EAS exome AF: 0.533

Gnomad FIN exome AF: 0.362

Gnomad NFE exome AF: 0.557

Gnomad OTH exome AF: 0.551

GnomAD4 exome AF: 0.562 AC: 814350 AN: 1449082 Hom.: 231029 Cov.: 29 AF XY: 0.564 AC XY: 406376 AN XY: 720494

African (AFR) AF: 0.680 AC: 22383 AN: 32926

American (AMR) AF: 0.599 AC: 25577 AN: 42692

Ashkenazi Jewish (ASJ) AF: 0.515 AC: 13262 AN: 25728

East Asian (EAS) AF: 0.487 AC: 19275 AN: 39590

South Asian (SAS) AF: 0.614 AC: 51689 AN: 84160

European-Finnish (FIN) AF: 0.376 AC: 19934 AN: 53078

Middle Eastern (MID) AF: 0.661 AC: 3780 AN: 5720

European-Non Finnish (NFE) AF: 0.565 AC: 624467 AN: 1105252

Other (OTH) AF: 0.567 AC: 33983 AN: 59936

GnomAD4 genome AF: 0.574 AC: 87211 AN: 152046 Hom.: 25386 Cov.: 33 AF XY: 0.563 AC XY: 41864 AN XY: 74324

African (AFR) AF: 0.664 AC: 27556 AN: 41486

American (AMR) AF: 0.562 AC: 8579 AN: 15264

Ashkenazi Jewish (ASJ) AF: 0.509 AC: 1767 AN: 3472

East Asian (EAS) AF: 0.507 AC: 2616 AN: 5158

South Asian (SAS) AF: 0.588 AC: 2831 AN: 4816

European-Finnish (FIN) AF: 0.364 AC: 3856 AN: 10584

Middle Eastern (MID) AF: 0.697 AC: 205 AN: 294

European-Non Finnish (NFE) AF: 0.560 AC: 38044 AN: 67956

Other (OTH) AF: 0.586 AC: 1232 AN: 2104

Alfa AF: 0.564 Hom.: 101924

Bravo AF: 0.597

Asia WGS AF: 0.528 AC: 1836 AN: 3478

EpiCase AF: 0.575

EpiControl AF: 0.576

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	0.78
DANN	Benign	0.56
PhyloP100		-1.8
Mutation Taster		=99/1	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.00015
dbscSNV1_RF	Benign	0.020
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: rs7909832; hg19: chr10-16556710; COSMIC: COSV54345061; COSMIC: COSV54345061;