2-121530637-C-T

Position:

• chr2-121530637-C-T

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.196-312G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0433 in 530,882 control chromosomes in the GnomAD database, including 651 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.038 (157 hom., cov: 33)
  • Exomes 𝑓: 0.046 (494 hom.)
• Consequence: CLASP1 NM_001395891.1 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.375

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=-0.72).
• BP6: Variant 2-121530637-C-T is Benign according to our data. Variant chr2-121530637-C-T is described in ClinVar as [Benign]. Clinvar id is 1183560.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0521 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CLASP1	NM_001395891.1	c.196-312G>A		intron_variant		ENST00000696935.1	NP_001382820.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CLASP1	ENST00000696935.1	c.196-312G>A		intron_variant			NM_001395891.1	ENSP00000512981.1

Frequencies

GnomAD3 genomes AF: 0.0377 AC: 5745 AN: 152258 Hom.: 157 Cov.: 33

Gnomad AFR AF: 0.00878

Gnomad AMI AF: 0.114

Gnomad AMR AF: 0.0288

Gnomad ASJ AF: 0.0766

Gnomad EAS AF: 0.000961

Gnomad SAS AF: 0.0459

Gnomad FIN AF: 0.0567

Gnomad MID AF: 0.0791

Gnomad NFE AF: 0.0535

Gnomad OTH AF: 0.0354

GnomAD4 exome AF: 0.0456 AC: 17264 AN: 378506 Hom.: 494 Cov.: 0 AF XY: 0.0463 AC XY: 9124 AN XY: 197060

Gnomad4 AFR exome AF: 0.00848

Gnomad4 AMR exome AF: 0.0182

Gnomad4 ASJ exome AF: 0.0705

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0486

Gnomad4 FIN exome AF: 0.0547

Gnomad4 NFE exome AF: 0.0525

Gnomad4 OTH exome AF: 0.0430

GnomAD4 genome AF: 0.0377 AC: 5746 AN: 152376 Hom.: 157 Cov.: 33 AF XY: 0.0373 AC XY: 2778 AN XY: 74508

Gnomad4 AFR AF: 0.00875

Gnomad4 AMR AF: 0.0287

Gnomad4 ASJ AF: 0.0766

Gnomad4 EAS AF: 0.000963

Gnomad4 SAS AF: 0.0464

Gnomad4 FIN AF: 0.0567

Gnomad4 NFE AF: 0.0535

Gnomad4 OTH AF: 0.0350

Alfa AF: 0.0393 Hom.: 18

Bravo AF: 0.0341

Asia WGS AF: 0.0180 AC: 65 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Jul 09, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.72
CADD	Benign	10
DANN	Benign	0.94

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

LitVar

Other links and lift over

dbSNP: rs146403563; hg19: chr2-122288213;