rs144957722

Variant names:

• chr2-121367797-G-T
• rs144957722
• NM_001395891.1:c.3740C>A

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_Strong BP6 BA1

The NM_001395891.1(CLASP1):​c.3740C>A​(p.Thr1247Asn) variant causes a missense change. The variant allele was found at a frequency of 0.00371 in 1,613,780 control chromosomes in the GnomAD database, including 267 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (no stars).

• Frequency:
  • Genomes: 𝑓 0.0072 (44 hom., cov: 32)
  • Exomes 𝑓: 0.0033 (223 hom.)
• Consequence: CLASP1 NM_001395891.1 missense
• Clinical Significance: Benign no assertion criteria provided B:1
• Conservation: PhyloP100: 5.28
• Publications: 6 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 -13 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0016407967).
• BP6: Variant 2-121367797-G-T is Benign according to our data. Variant chr2-121367797-G-T is described in ClinVar as Benign. ClinVar VariationId is 3037345.Status of the report is no_assertion_criteria_provided, 0 stars.
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.0593 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.3740C>A	p.Thr1247Asn	missense	Exon 36 of 41	NP_001382820.1	A0A8V8TLP7
	CLASP1	NM_015282.3		c.3677C>A	p.Thr1226Asn	missense	Exon 35 of 40	NP_056097.1	Q7Z460-1
	CLASP1	NM_001378003.1		c.3581C>A	p.Thr1194Asn	missense	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.3740C>A	p.Thr1247Asn	missense	Exon 36 of 41	ENSP00000512981.1	A0A8V8TLP7
	CLASP1	ENST00000263710.8	TSL:5	c.3677C>A	p.Thr1226Asn	missense	Exon 35 of 40	ENSP00000263710.4	Q7Z460-1
	CLASP1	ENST00000961911.1		c.3620C>A	p.Thr1207Asn	missense	Exon 35 of 40	ENSP00000631970.1

Frequencies

GnomAD3 genomes AF: 0.00724 AC: 1102 AN: 152208 Hom.: 44 Cov.: 32

Gnomad AFR AF: 0.00162

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0625

Gnomad ASJ AF: 0.000288

Gnomad EAS AF: 0.0104

Gnomad SAS AF: 0.000827

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000118

Gnomad OTH AF: 0.00622

GnomAD2 exomes AF: 0.0142 AC: 3521 AN: 248660 AF XY: 0.0106

Gnomad AFR exome AF: 0.000971

Gnomad AMR exome AF: 0.0916

Gnomad ASJ exome AF: 0.000299

Gnomad EAS exome AF: 0.0149

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000355

Gnomad OTH exome AF: 0.00878

GnomAD4 exome AF: 0.00334 AC: 4880 AN: 1461454 Hom.: 223 Cov.: 32 AF XY: 0.00285 AC XY: 2074 AN XY: 727028

African (AFR) AF: 0.000926 AC: 31 AN: 33480

American (AMR) AF: 0.0908 AC: 4062 AN: 44720

Ashkenazi Jewish (ASJ) AF: 0.000344 AC: 9 AN: 26134

East Asian (EAS) AF: 0.0117 AC: 463 AN: 39700

South Asian (SAS) AF: 0.000417 AC: 36 AN: 86258

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53190

Middle Eastern (MID) AF: 0.000867 AC: 5 AN: 5766

European-Non Finnish (NFE) AF: 0.0000396 AC: 44 AN: 1111846

Other (OTH) AF: 0.00381 AC: 230 AN: 60360

GnomAD4 genome AF: 0.00725 AC: 1104 AN: 152326 Hom.: 44 Cov.: 32 AF XY: 0.00798 AC XY: 594 AN XY: 74476

African (AFR) AF: 0.00161 AC: 67 AN: 41586

American (AMR) AF: 0.0625 AC: 957 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.000288 AC: 1 AN: 3472

East Asian (EAS) AF: 0.0104 AC: 54 AN: 5174

South Asian (SAS) AF: 0.000828 AC: 4 AN: 4830

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10620

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.000118 AC: 8 AN: 68026

Other (OTH) AF: 0.00616 AC: 13 AN: 2112

Alfa AF: 0.00183 Hom.: 22

Bravo AF: 0.0122

ESP6500AA AF: 0.000767 AC: 3

ESP6500EA AF: 0.000241 AC: 2

ExAC AF: 0.0104 AC: 1252

Asia WGS AF: 0.0110 AC: 39 AN: 3478

EpiCase AF: 0.00

EpiControl AF: 0.0000593

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: no assertion criteria provided

Pathogenic	VUS	Benign	Condition
-	-	1	CLASP1-related disorder (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.12
BayesDel_addAF	Benign	-0.60	T
BayesDel_noAF	Benign	-0.56
CADD	Benign	21
DANN	Benign	0.51
DEOGEN2	Benign	0.030	T
Eigen	Benign	-0.23
Eigen_PC	Benign	-0.069
FATHMM_MKL	Pathogenic	0.97	D
LIST_S2	Uncertain	0.96	D
MetaRNN	Benign	0.0016	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.81	L
PhyloP100		5.3
PrimateAI	Benign	0.42	T
PROVEAN	Benign	-0.74	N
REVEL	Benign	0.054
Sift	Benign	0.41	T
Sift4G	Benign	0.25	T
Polyphen		0.15	B
Vest4		0.31
MPC		0.46
ClinPred		0.022	T
GERP RS		5.1
Varity_R		0.12
gMVP		0.27
Mutation Taster		=99/1	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs144957722; hg19: chr2-122125373;