2-121530617-C-A

Variant names:

• chr2-121530617-C-A
• rs111756154
• NM_001395891.1:c.196-292G>T

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 0 publications found

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

Our verdict: Benign. The variant received -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 VariationId 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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001395891.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CLASP1	NM_001395891.1	MANE Select	c.196-292G>T		intron	N/A	NP_001382820.1	A0A8V8TLP7
	CLASP1	NM_015282.3		c.196-292G>T		intron	N/A	NP_056097.1	Q7Z460-1
	CLASP1	NM_001378003.1		c.196-292G>T		intron	N/A	NP_001364932.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CLASP1	ENST00000696935.1	MANE Select	c.196-292G>T		intron	N/A	ENSP00000512981.1	A0A8V8TLP7
	CLASP1	ENST00000263710.8	TSL:5	c.196-292G>T		intron	N/A	ENSP00000263710.4	Q7Z460-1
	CLASP1	ENST00000961911.1		c.196-292G>T		intron	N/A	ENSP00000631970.1

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

African (AFR) AF: 0.0186 AC: 211 AN: 11358

American (AMR) AF: 0.0460 AC: 692 AN: 15028

Ashkenazi Jewish (ASJ) AF: 0.0546 AC: 660 AN: 12088

East Asian (EAS) AF: 0.115 AC: 3362 AN: 29184

South Asian (SAS) AF: 0.0486 AC: 1517 AN: 31236

European-Finnish (FIN) AF: 0.0288 AC: 768 AN: 26686

Middle Eastern (MID) AF: 0.0248 AC: 42 AN: 1692

European-Non Finnish (NFE) AF: 0.0437 AC: 9983 AN: 228414

Other (OTH) AF: 0.0470 AC: 1060 AN: 22558

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

African (AFR) AF: 0.0196 AC: 816 AN: 41586

American (AMR) AF: 0.0383 AC: 587 AN: 15310

Ashkenazi Jewish (ASJ) AF: 0.0628 AC: 218 AN: 3470

East Asian (EAS) AF: 0.139 AC: 723 AN: 5186

South Asian (SAS) AF: 0.0538 AC: 260 AN: 4830

European-Finnish (FIN) AF: 0.0248 AC: 263 AN: 10622

Middle Eastern (MID) AF: 0.0306 AC: 9 AN: 294

European-Non Finnish (NFE) AF: 0.0422 AC: 2868 AN: 68024

Other (OTH) AF: 0.0308 AC: 65 AN: 2112

Alfa AF: 0.0376 Hom.: 17

Bravo AF: 0.0400

Asia WGS AF: 0.0670 AC: 236 AN: 3478

ClinVar

ClinVar submissions as Germline

Significance: Likely benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.63
CADD	Benign	6.9
DANN	Benign	0.82
PhyloP100		-0.021
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs111756154; hg19: chr2-122288193;