2-121530869-C-T

Variant names:

• chr2-121530869-C-T
• rs74790826
• NM_001395891.1:c.196-544G>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.196-544G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0451 in 678,710 control chromosomes in the GnomAD database, including 903 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.039 (157 hom., cov: 32)
  • Exomes 𝑓: 0.047 (746 hom.)
• Consequence: CLASP1 NM_001395891.1 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:4
• Conservation: PhyloP100: -7.95

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)

RNU4ATAC (HGNC:34016): (RNA, U4atac small nuclear) The small nuclear RNA (snRNA) encoded by this gene is part of the U12-dependent minor spliceosome complex. In addition to the encoded RNA, this ribonucleoprotein complex consists of U11, U12, U5, and U6atac snRNAs. The U12-dependent spliceosome acts on approximately 700 specific introns in the human genome. Defects in this gene are a cause of microcephalic osteodysplastic primordial dwarfism type 1 (MOPD). [provided by RefSeq, Jul 2011]

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.96).
• BP6: Variant 2-121530869-C-T is Benign according to our data. Variant chr2-121530869-C-T is described in ClinVar as [Benign]. Clinvar id is 1274763.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.13 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CLASP1	NM_001395891.1	c.196-544G>A		intron_variant	Intron 2 of 40	ENST00000696935.1	NP_001382820.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CLASP1	ENST00000696935.1	c.196-544G>A		intron_variant	Intron 2 of 40		NM_001395891.1	ENSP00000512981.1

Frequencies

GnomAD3 genomes AF: 0.0385 AC: 5861 AN: 152190 Hom.: 156 Cov.: 32

Gnomad AFR AF: 0.0196

Gnomad AMI AF: 0.0526

Gnomad AMR AF: 0.0381

Gnomad ASJ AF: 0.0637

Gnomad EAS AF: 0.139

Gnomad SAS AF: 0.0536

Gnomad FIN AF: 0.0248

Gnomad MID AF: 0.0285

Gnomad NFE AF: 0.0423

Gnomad OTH AF: 0.0311

GnomAD3 exomes AF: 0.0512 AC: 6485 AN: 126736 Hom.: 209 AF XY: 0.0505 AC XY: 3499 AN XY: 69236

Gnomad AFR exome AF: 0.0156

Gnomad AMR exome AF: 0.0526

Gnomad ASJ exome AF: 0.0596

Gnomad EAS exome AF: 0.131

Gnomad SAS exome AF: 0.0455

Gnomad FIN exome AF: 0.0268

Gnomad NFE exome AF: 0.0420

Gnomad OTH exome AF: 0.0487

GnomAD4 exome AF: 0.0470 AC: 24755 AN: 526402 Hom.: 746 Cov.: 0 AF XY: 0.0469 AC XY: 13216 AN XY: 281904

Gnomad4 AFR exome AF: 0.0189

Gnomad4 AMR exome AF: 0.0508

Gnomad4 ASJ exome AF: 0.0566

Gnomad4 EAS exome AF: 0.115

Gnomad4 SAS exome AF: 0.0470

Gnomad4 FIN exome AF: 0.0285

Gnomad4 NFE exome AF: 0.0425

Gnomad4 OTH exome AF: 0.0463

GnomAD4 genome AF: 0.0385 AC: 5865 AN: 152308 Hom.: 157 Cov.: 32 AF XY: 0.0377 AC XY: 2808 AN XY: 74474

Gnomad4 AFR AF: 0.0197

Gnomad4 AMR AF: 0.0383

Gnomad4 ASJ AF: 0.0637

Gnomad4 EAS AF: 0.139

Gnomad4 SAS AF: 0.0533

Gnomad4 FIN AF: 0.0248

Gnomad4 NFE AF: 0.0423

Gnomad4 OTH AF: 0.0308

Alfa AF: 0.0230 Hom.: 10

Bravo AF: 0.0401

Asia WGS AF: 0.0670 AC: 235 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Jul 10, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

RNU4ATAC-related disorder Benign:1

Mar 20, 2019

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

CLASP1-related disorder Benign:1

Mar 20, 2019

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	0.0010
DANN	Benign	0.75

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs74790826; hg19: chr2-122288445;