12-122274172-T-TA

Position:

• chr12-122274172-T-TA

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP6_Moderate BS2

The NM_001247997.2(CLIP1):​c.3967-11_3967-10insT variant causes a splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00333 in 1,404,870 control chromosomes in the GnomAD database, including 1 homozygotes. Variant has been reported in ClinVar as Benign (★). There are indicators that this mutation may affect the branch point..

• Frequency:
  • Genomes: 𝑓 0.0030 (1 hom., cov: 32)
  • Exomes 𝑓: 0.0034 (0 hom.)
• Consequence: CLIP1 NM_001247997.2 splice_polypyrimidine_tract, intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -4.14

Genes affected

CLIP1 (HGNC:10461): (CAP-Gly domain containing linker protein 1) The protein encoded by this gene links endocytic vesicles to microtubules. This gene is highly expressed in Reed-Sternberg cells of Hodgkin disease. Several transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Oct 2011]

ACMG classification

Verdict is Likely_benign. Variant got -6 ACMG points.

• BP6: Variant 12-122274172-T-TA is Benign according to our data. Variant chr12-122274172-T-TA is described in ClinVar as [Benign]. Clinvar id is 1336261.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High AC in GnomAd4 at 444 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CLIP1	NM_001247997.2	c.3967-11_3967-10insT		splice_polypyrimidine_tract_variant, intron_variant		ENST00000620786.5	NP_001234926.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CLIP1	ENST00000620786.5	c.3967-11_3967-10insT		splice_polypyrimidine_tract_variant, intron_variant		5	NM_001247997.2	ENSP00000479322	A1

Frequencies

GnomAD3 genomes AF: 0.00295 AC: 442 AN: 149608 Hom.: 1 Cov.: 32

Gnomad AFR AF: 0.00887

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00194

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00330

Gnomad SAS AF: 0.00105

Gnomad FIN AF: 0.0000999

Gnomad MID AF: 0.00318

Gnomad NFE AF: 0.000327

Gnomad OTH AF: 0.00245

GnomAD4 exome AF: 0.00337 AC: 4231 AN: 1255164 Hom.: 0 Cov.: 24 AF XY: 0.00320 AC XY: 1999 AN XY: 624512

Gnomad4 AFR exome AF: 0.0114

Gnomad4 AMR exome AF: 0.00323

Gnomad4 ASJ exome AF: 0.00276

Gnomad4 EAS exome AF: 0.00315

Gnomad4 SAS exome AF: 0.00170

Gnomad4 FIN exome AF: 0.00245

Gnomad4 NFE exome AF: 0.00333

Gnomad4 OTH exome AF: 0.00342

GnomAD4 genome AF: 0.00297 AC: 444 AN: 149706 Hom.: 1 Cov.: 32 AF XY: 0.00322 AC XY: 235 AN XY: 73064

Gnomad4 AFR AF: 0.00889

Gnomad4 AMR AF: 0.00194

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00331

Gnomad4 SAS AF: 0.00105

Gnomad4 FIN AF: 0.0000999

Gnomad4 NFE AF: 0.000327

Gnomad4 OTH AF: 0.00243

Bravo AF: 0.00315

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Benign:1

Benign, criteria provided, single submitter

clinical testing

Genetic Services Laboratory, University of Chicago

Sep 23, 2019

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BranchPoint Hunter		4.0

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

Publications

LitVar

Other links and lift over

dbSNP: rs376224001; hg19: chr12-122758719;