chr2-121530617-C-A

Position:

• chr2-121530617-C-A

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_001395891.1(CLASP1):​c.196-292G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0455 in 530,590 control chromosomes in the GnomAD database, including 731 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.038 (159 hom., cov: 33)
  • Exomes 𝑓: 0.048 (572 hom.)
• Consequence: CLASP1 NM_001395891.1 intron
• Clinical Significance: Likely benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.0210

Genes affected

CLASP1 (HGNC:17088): (cytoplasmic linker associated protein 1) CLASPs, such as CLASP1, are nonmotor microtubule-associated proteins that interact with CLIPs (e.g., CLIP170; MIM 179838). CLASP1 is involved in the regulation of microtubule dynamics at the kinetochore and throughout the spindle (Maiato et al., 2003 [PubMed 12837247]).[supplied by OMIM, Mar 2008]

CLASP1-AS1 (HGNC:55328): (CLASP1 antisense RNA 1)

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.63).
• BP6: Variant 2-121530617-C-A is Benign according to our data. Variant chr2-121530617-C-A is described in ClinVar as [Likely_benign]. Clinvar id is 1202360.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.131 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CLASP1	NM_001395891.1	c.196-292G>T		intron_variant		ENST00000696935.1	NP_001382820.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CLASP1	ENST00000696935.1	c.196-292G>T		intron_variant			NM_001395891.1	ENSP00000512981.1

Frequencies

GnomAD3 genomes AF: 0.0384 AC: 5853 AN: 152228 Hom.: 158 Cov.: 33

Gnomad AFR AF: 0.0196

Gnomad AMI AF: 0.0526

Gnomad AMR AF: 0.0382

Gnomad ASJ AF: 0.0628

Gnomad EAS AF: 0.139

Gnomad SAS AF: 0.0542

Gnomad FIN AF: 0.0248

Gnomad MID AF: 0.0285

Gnomad NFE AF: 0.0422

Gnomad OTH AF: 0.0311

GnomAD4 exome AF: 0.0484 AC: 18295 AN: 378244 Hom.: 572 Cov.: 0 AF XY: 0.0484 AC XY: 9541 AN XY: 196972

Gnomad4 AFR exome AF: 0.0186

Gnomad4 AMR exome AF: 0.0460

Gnomad4 ASJ exome AF: 0.0546

Gnomad4 EAS exome AF: 0.115

Gnomad4 SAS exome AF: 0.0486

Gnomad4 FIN exome AF: 0.0288

Gnomad4 NFE exome AF: 0.0437

Gnomad4 OTH exome AF: 0.0470

GnomAD4 genome AF: 0.0384 AC: 5857 AN: 152346 Hom.: 159 Cov.: 33 AF XY: 0.0377 AC XY: 2808 AN XY: 74496

Gnomad4 AFR AF: 0.0196

Gnomad4 AMR AF: 0.0383

Gnomad4 ASJ AF: 0.0628

Gnomad4 EAS AF: 0.139

Gnomad4 SAS AF: 0.0538

Gnomad4 FIN AF: 0.0248

Gnomad4 NFE AF: 0.0422

Gnomad4 OTH AF: 0.0308

Alfa AF: 0.0367 Hom.: 16

Bravo AF: 0.0400

Asia WGS AF: 0.0670 AC: 236 AN: 3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Likely benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Likely benign, criteria provided, single submitter	clinical testing	GeneDx	Jul 10, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.63
CADD	Benign	6.9
DANN	Benign	0.82

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.060		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: rs111756154; hg19: chr2-122288193;