12-122278196-T-C

Variant summary

Our verdict is Benign. Variant got -11 ACMG points: 0P and 11B. BP4_Strong BP6_Moderate BP7 BS2

The NM_001247997.2(CLIP1):c.3924A>G(p.Thr1308=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000631 in 1,598,150 control chromosomes in the GnomAD database, including 10 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.00051 (1 hom., cov: 30)
  • Exomes 𝑓: 0.00064 (9 hom.)
• Consequence: CLIP1 NM_001247997.2 synonymous
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.0370

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 Benign. Variant got -11 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.64).
• BP6: Variant 12-122278196-T-C is Benign according to our data. Variant chr12-122278196-T-C is described in ClinVar as [Benign]. Clinvar id is 717357.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=-0.037 with no splicing effect.
• BS2: High AC in GnomAd at 77 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CLIP1	NM_001247997.2	c.3924A>G	p.Thr1308=	synonymous_variant	24/26	ENST00000620786.5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CLIP1	ENST00000620786.5	c.3924A>G	p.Thr1308=	synonymous_variant	24/26	5	NM_001247997.2	A1

Frequencies

GnomAD3 genomes AF: 0.000519 AC: 77 AN: 148278 Hom.: 1 Cov.: 30

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00954

Gnomad EAS AF: 0.00787

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000443

Gnomad OTH AF: 0.000490

GnomAD3 exomes AF: 0.000989 AC: 237 AN: 239738 Hom.: 2 AF XY: 0.00102 AC XY: 133 AN XY: 130282

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.0000595

Gnomad ASJ exome AF: 0.00981

Gnomad EAS exome AF: 0.00636

Gnomad SAS exome AF: 0.000135

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000134

Gnomad OTH exome AF: 0.00117

GnomAD4 exome AF: 0.000644 AC: 933 AN: 1449758 Hom.: 9 Cov.: 31 AF XY: 0.000628 AC XY: 453 AN XY: 721586

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.0000680

Gnomad4 ASJ exome AF: 0.0102

Gnomad4 EAS exome AF: 0.0139

Gnomad4 SAS exome AF: 0.000140

Gnomad4 FIN exome AF: 0.0000222

Gnomad4 NFE exome AF: 0.0000441

Gnomad4 OTH exome AF: 0.000848

GnomAD4 genome AF: 0.000512 AC: 76 AN: 148392 Hom.: 1 Cov.: 30 AF XY: 0.000470 AC XY: 34 AN XY: 72364

Gnomad4 AFR AF: 0.00

Gnomad4 AMR AF: 0.00

Gnomad4 ASJ AF: 0.00954

Gnomad4 EAS AF: 0.00769

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000443

Gnomad4 OTH AF: 0.000484

Alfa AF: 0.00130 Hom.: 1

Bravo AF: 0.000555

Asia WGS AF: 0.00404 AC: 14 AN: 3476

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Dec 05, 2017

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.64
Cadd	Benign	5.9
Dann	Benign	0.54
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.12		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: rs78676307; hg19: chr12-122762743;