rs777457137

Variant names:

• chr2-121530890-T-TA
• rs777457137
• NM_001395891.1:c.196-566_196-565insT

Your query was ambiguous. Multiple possible variants found:

• chr2-121530890-T-TA
• chr2-121530890-T-TG

Variant summary

Our verdict is Likely benign. The variant received -1 ACMG points: 0P and 1B. BS2_Supporting

The NM_001395891.1(CLASP1):​c.196-566_196-565insT variant causes a intron change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000317 in 693,700 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000039 (0 hom., cov: 32)
  • Exomes 𝑓: 0.000030 (0 hom.)
• Consequence: CLASP1 NM_001395891.1 intron
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 7.54
• Publications: 1 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 -1 ACMG points.

• BS2: High AC in GnomAd4 at 6 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.196-566_196-565insT		intron	N/A	NP_001382820.1	A0A8V8TLP7
	RNU4ATAC	NR_023343.3	MANE Select	n.11_12insA		non_coding_transcript_exon	Exon 1 of 1
	CLASP1	NM_015282.3		c.196-566_196-565insT		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.196-566_196-565insT		intron	N/A	ENSP00000512981.1	A0A8V8TLP7
	RNU4ATAC	ENST00000580972.2	TSL:6 MANE Select	n.11_12insA		non_coding_transcript_exon	Exon 1 of 1
	CLASP1	ENST00000263710.8	TSL:5	c.196-566_196-565insT		intron	N/A	ENSP00000263710.4	Q7Z460-1

Frequencies

GnomAD3 genomes AF: 0.0000394 AC: 6 AN: 152162 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.0000241

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000735

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000231 AC: 3 AN: 129772 AF XY: 0.0000141

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: 0.0000202

Gnomad OTH exome AF: 0.000251

GnomAD4 exome AF: 0.0000296 AC: 16 AN: 541420 Hom.: 0 Cov.: 0 AF XY: 0.0000308 AC XY: 9 AN XY: 292090

African (AFR) AF: 0.00 AC: 0 AN: 15592

American (AMR) AF: 0.00 AC: 0 AN: 34444

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 19922

East Asian (EAS) AF: 0.0000314 AC: 1 AN: 31894

South Asian (SAS) AF: 0.0000480 AC: 3 AN: 62458

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 33120

Middle Eastern (MID) AF: 0.000413 AC: 1 AN: 2424

European-Non Finnish (NFE) AF: 0.0000353 AC: 11 AN: 311486

Other (OTH) AF: 0.00 AC: 0 AN: 30080

GnomAD4 genome AF: 0.0000394 AC: 6 AN: 152280 Hom.: 0 Cov.: 32 AF XY: 0.0000403 AC XY: 3 AN XY: 74458

African (AFR) AF: 0.0000241 AC: 1 AN: 41570

American (AMR) AF: 0.00 AC: 0 AN: 15304

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

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

South Asian (SAS) AF: 0.00 AC: 0 AN: 4822

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10612

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

European-Non Finnish (NFE) AF: 0.0000735 AC: 5 AN: 68008

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

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.0000227

ClinVar

ClinVar submissions as Germline

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		7.5

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: rs777457137; hg19: chr2-122288466;