chr10-16514711-T-C

Position:

• chr10-16514711-T-C

Variant summary

Our verdict is Benign. Variant got -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

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:):

ACMG classification

Verdict is Benign. Variant got -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/exons	MANE	Protein	UniProt
C1QL3	NM_001010908.2	c.589-4A>G		splice_region_variant, intron_variant		ENST00000298943.4	NP_001010908.1
PTER	XR_007062017.1	n.2492-2005T>C		intron_variant
PTER	XR_007062018.1	n.2103-2005T>C		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
C1QL3	ENST00000298943.4	c.589-4A>G		splice_region_variant, intron_variant		1	NM_001010908.2	ENSP00000298943.3

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

GnomAD3 exomes AF: 0.556 AC: 134854 AN: 242592 Hom.: 38171 AF XY: 0.557 AC XY: 72870 AN XY: 130910

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 SAS exome AF: 0.608

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

Gnomad4 AFR exome AF: 0.680

Gnomad4 AMR exome AF: 0.599

Gnomad4 ASJ exome AF: 0.515

Gnomad4 EAS exome AF: 0.487

Gnomad4 SAS exome AF: 0.614

Gnomad4 FIN exome AF: 0.376

Gnomad4 NFE exome AF: 0.565

Gnomad4 OTH exome AF: 0.567

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

Gnomad4 AFR AF: 0.664

Gnomad4 AMR AF: 0.562

Gnomad4 ASJ AF: 0.509

Gnomad4 EAS AF: 0.507

Gnomad4 SAS AF: 0.588

Gnomad4 FIN AF: 0.364

Gnomad4 NFE AF: 0.560

Gnomad4 OTH AF: 0.586

Alfa AF: 0.562 Hom.: 53226

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

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

Publications

LitVar

Other links and lift over

dbSNP: rs7909832; hg19: chr10-16556710; COSMIC: COSV54345061; COSMIC: COSV54345061;