2-121367637-G-A

Variant names:

• chr2-121367637-G-A
• rs116176232
• NM_001395891.1:c.3900C>T

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BS1 BS2

The NM_001395891.1(CLASP1):​c.3900C>T​(p.Thr1300Thr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00776 in 1,614,030 control chromosomes in the GnomAD database, including 80 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0071 (9 hom., cov: 32)
  • Exomes 𝑓: 0.0078 (71 hom.)
• Consequence: CLASP1 NM_001395891.1 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -1.31
• Publications: 4 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 Gene-Disease associations (from GenCC):

• focal epilepsy

  Inheritance: AD Classification: LIMITED Submitted by: Ambry Genetics
• complex neurodevelopmental disorder

  Inheritance: AD Classification: NO_KNOWN Submitted by: Illumina

ACMG classification

Our verdict: Benign. The variant received -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.8).
• BP6: Variant 2-121367637-G-A is Benign according to our data. Variant chr2-121367637-G-A is described in ClinVar as Benign. ClinVar VariationId is 785851.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-1.31 with no splicing effect.
• BS1: Variant frequency is greater than expected in population nfe. GnomAd4 allele frequency = 0.00707 (1077/152320) while in subpopulation NFE AF = 0.0095 (646/68032). AF 95% confidence interval is 0.00889. There are 9 homozygotes in GnomAd4. There are 508 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.
• BS2: High AC in GnomAd4 at 1077 AD gene.

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.3900C>T	p.Thr1300Thr	synonymous	Exon 36 of 41	NP_001382820.1	A0A8V8TLP7
	CLASP1	NM_015282.3		c.3837C>T	p.Thr1279Thr	synonymous	Exon 35 of 40	NP_056097.1	Q7Z460-1
	CLASP1	NM_001378003.1		c.3741C>T	p.Thr1247Thr	synonymous	Exon 34 of 39	NP_001364932.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CLASP1	ENST00000696935.1	MANE Select	c.3900C>T	p.Thr1300Thr	synonymous	Exon 36 of 41	ENSP00000512981.1	A0A8V8TLP7
	CLASP1	ENST00000263710.8	TSL:5	c.3837C>T	p.Thr1279Thr	synonymous	Exon 35 of 40	ENSP00000263710.4	Q7Z460-1
	CLASP1	ENST00000961911.1		c.3780C>T	p.Thr1260Thr	synonymous	Exon 35 of 40	ENSP00000631970.1

Frequencies

GnomAD3 genomes AF: 0.00708 AC: 1077 AN: 152202 Hom.: 9 Cov.: 32

Gnomad AFR AF: 0.00166

Gnomad AMI AF: 0.0241

Gnomad AMR AF: 0.00792

Gnomad ASJ AF: 0.0207

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00311

Gnomad FIN AF: 0.00960

Gnomad MID AF: 0.0601

Gnomad NFE AF: 0.00949

Gnomad OTH AF: 0.00527

GnomAD2 exomes AF: 0.00832 AC: 2074 AN: 249302 AF XY: 0.00877

Gnomad AFR exome AF: 0.00187

Gnomad AMR exome AF: 0.00713

Gnomad ASJ exome AF: 0.0211

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00928

Gnomad NFE exome AF: 0.0108

Gnomad OTH exome AF: 0.00941

GnomAD4 exome AF: 0.00783 AC: 11445 AN: 1461710 Hom.: 71 Cov.: 32 AF XY: 0.00783 AC XY: 5697 AN XY: 727138

African (AFR) AF: 0.00167 AC: 56 AN: 33480

American (AMR) AF: 0.00682 AC: 305 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.0233 AC: 608 AN: 26136

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.00365 AC: 315 AN: 86258

European-Finnish (FIN) AF: 0.0103 AC: 550 AN: 53402

Middle Eastern (MID) AF: 0.0151 AC: 87 AN: 5768

European-Non Finnish (NFE) AF: 0.00808 AC: 8989 AN: 1111868

Other (OTH) AF: 0.00886 AC: 535 AN: 60374

GnomAD4 genome AF: 0.00707 AC: 1077 AN: 152320 Hom.: 9 Cov.: 32 AF XY: 0.00682 AC XY: 508 AN XY: 74476

African (AFR) AF: 0.00166 AC: 69 AN: 41578

American (AMR) AF: 0.00791 AC: 121 AN: 15306

Ashkenazi Jewish (ASJ) AF: 0.0207 AC: 72 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5176

South Asian (SAS) AF: 0.00332 AC: 16 AN: 4820

European-Finnish (FIN) AF: 0.00960 AC: 102 AN: 10622

Middle Eastern (MID) AF: 0.0612 AC: 18 AN: 294

European-Non Finnish (NFE) AF: 0.00950 AC: 646 AN: 68032

Other (OTH) AF: 0.00521 AC: 11 AN: 2110

Alfa AF: 0.00968 Hom.: 4

Bravo AF: 0.00685

Asia WGS AF: 0.00144 AC: 5 AN: 3478

EpiCase AF: 0.0113

EpiControl AF: 0.0104

ClinVar

ClinVar submissions

Significance: 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	-0.80
CADD	Benign	0.54
DANN	Benign	0.66
PhyloP100		-1.3
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Mutation Taster		=98/2	polymorphism

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

Other links and lift over

dbSNP: rs116176232; hg19: chr2-122125213;