rs533487249

Variant names:

• chr2-121530884-A-C
• rs533487249
• NM_001395891.1:c.196-559T>G

Your query was ambiguous. Multiple possible variants found:

• chr2-121530884-A-C
• chr2-121530884-A-G
• chr2-121530884-A-T

Variant summary

Our verdict is Likely benign. The variant received -3 ACMG points: 0P and 3B. BP4_Moderate BS2_Supporting

The NM_001395891.1(CLASP1):​c.196-559T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000144 in 692,676 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000020 (0 hom., cov: 33)
  • Exomes 𝑓: 0.000013 (0 hom.)
• Consequence: CLASP1 NM_001395891.1 intron
• Clinical Significance: Uncertain significance criteria provided, single submitter P:1 U:1
• Conservation: PhyloP100: 0.769
• 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]

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]

CLASP1-AS1 (HGNC:55328): (CLASP1 antisense RNA 1)

ACMG classification

Our verdict: Likely_benign. The variant received -3 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.42).
• BS2: High AC in GnomAdExome4 at 7 AD gene. Variant has AC lower than other variant known as pathogenic in the gene, so the strength is limited to Supporting.

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.196-559T>G		intron	N/A	NP_001382820.1	A0A8V8TLP7
	RNU4ATAC	NR_023343.3	MANE Select	n.5A>C		non_coding_transcript_exon	Exon 1 of 1
	CLASP1	NM_015282.3		c.196-559T>G		intron	N/A	NP_056097.1	Q7Z460-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CLASP1	ENST00000696935.1	MANE Select	c.196-559T>G		intron	N/A	ENSP00000512981.1	A0A8V8TLP7
	RNU4ATAC	ENST00000580972.2	TSL:6 MANE Select	n.5A>C		non_coding_transcript_exon	Exon 1 of 1
	CLASP1	ENST00000263710.8	TSL:5	c.196-559T>G		intron	N/A	ENSP00000263710.4	Q7Z460-1

Frequencies

GnomAD3 genomes AF: 0.0000197 AC: 3 AN: 152082 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000654

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000147

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000154 AC: 2 AN: 129496 AF XY: 0.00

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000203

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000130 AC: 7 AN: 540476 Hom.: 0 Cov.: 0 AF XY: 0.00000686 AC XY: 2 AN XY: 291478

African (AFR) AF: 0.00 AC: 0 AN: 15552

American (AMR) AF: 0.0000291 AC: 1 AN: 34334

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 19882

East Asian (EAS) AF: 0.00 AC: 0 AN: 31892

South Asian (SAS) AF: 0.00 AC: 0 AN: 62394

European-Finnish (FIN) AF: 0.0000302 AC: 1 AN: 33118

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 2422

European-Non Finnish (NFE) AF: 0.0000129 AC: 4 AN: 310862

Other (OTH) AF: 0.0000333 AC: 1 AN: 30020

GnomAD4 genome AF: 0.0000197 AC: 3 AN: 152200 Hom.: 0 Cov.: 33 AF XY: 0.0000269 AC XY: 2 AN XY: 74418

African (AFR) AF: 0.00 AC: 0 AN: 41522

American (AMR) AF: 0.0000654 AC: 1 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3468

East Asian (EAS) AF: 0.00 AC: 0 AN: 5168

South Asian (SAS) AF: 0.000208 AC: 1 AN: 4816

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10598

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

European-Non Finnish (NFE) AF: 0.0000147 AC: 1 AN: 68008

Other (OTH) AF: 0.00 AC: 0 AN: 2114

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.0000189

ClinVar

ClinVar submissions as Germline

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
1	-	-	Lowry-Wood syndrome (1)
-	1	-	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.42
CADD	Benign	16
DANN	Benign	0.79
PhyloP100		0.77
Mutation Taster		=2/98	disease causing

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: rs533487249; hg19: chr2-122288460;