12-122278196-T-C

Variant names:

• chr12-122278196-T-C
• rs78676307
• NM_001247997.2:c.3924A>G

Variant summary

Our verdict is Benign. The variant received -11 ACMG points: 0P and 11B. BP4_Strong BP6_Moderate BP7 BS2

The NM_001247997.2(CLIP1):​c.3924A>G​(p.Thr1308Thr) 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
• Publications: 2 publications found

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]

CLIP1 Gene-Disease associations (from GenCC):

• autosomal recessive non-syndromic intellectual disability

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
• intellectual disability

  Inheritance: AR Classification: LIMITED Submitted by: Ambry Genetics

ACMG classification

Our verdict: Benign. The variant received -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 VariationId 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 Homozygotes in GnomAdExome4 at 9 AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001247997.2. 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
	CLIP1	NM_001247997.2	MANE Select	c.3924A>G	p.Thr1308Thr	synonymous	Exon 24 of 26	NP_001234926.1	P30622-3
	CLIP1	NM_001389291.1		c.6054A>G	p.Thr2018Thr	synonymous	Exon 23 of 25	NP_001376220.1
	CLIP1	NM_002956.3		c.3891A>G	p.Thr1297Thr	synonymous	Exon 23 of 25	NP_002947.1	P30622-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CLIP1	ENST00000620786.5	TSL:5 MANE Select	c.3924A>G	p.Thr1308Thr	synonymous	Exon 24 of 26	ENSP00000479322.1	P30622-3
	CLIP1	ENST00000358808.6	TSL:1	c.3891A>G	p.Thr1297Thr	synonymous	Exon 23 of 25	ENSP00000351665.2	P30622-1
	CLIP1	ENST00000537178.5	TSL:1	c.3786A>G	p.Thr1262Thr	synonymous	Exon 22 of 24	ENSP00000445531.1	P30622-2

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

GnomAD2 exomes AF: 0.000989 AC: 237 AN: 239738 AF XY: 0.00102

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 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

African (AFR) AF: 0.00 AC: 0 AN: 33204

American (AMR) AF: 0.0000680 AC: 3 AN: 44134

Ashkenazi Jewish (ASJ) AF: 0.0102 AC: 265 AN: 26000

East Asian (EAS) AF: 0.0139 AC: 552 AN: 39662

South Asian (SAS) AF: 0.000140 AC: 12 AN: 85624

European-Finnish (FIN) AF: 0.0000222 AC: 1 AN: 44964

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5752

European-Non Finnish (NFE) AF: 0.0000441 AC: 49 AN: 1110258

Other (OTH) AF: 0.000848 AC: 51 AN: 60160

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

African (AFR) AF: 0.00 AC: 0 AN: 39078

American (AMR) AF: 0.00 AC: 0 AN: 14966

Ashkenazi Jewish (ASJ) AF: 0.00954 AC: 33 AN: 3458

East Asian (EAS) AF: 0.00769 AC: 39 AN: 5072

South Asian (SAS) AF: 0.00 AC: 0 AN: 4658

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10194

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

European-Non Finnish (NFE) AF: 0.0000443 AC: 3 AN: 67698

Other (OTH) AF: 0.000484 AC: 1 AN: 2064

Alfa AF: 0.000675 Hom.: 1

Bravo AF: 0.000555

Asia WGS AF: 0.00404 AC: 14 AN: 3476

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, single submitter

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

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.64
CADD	Benign	5.9
DANN	Benign	0.54
PhyloP100		-0.037
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Mutation Taster		=299/1	polymorphism

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

Other links and lift over

dbSNP: rs78676307; hg19: chr12-122762743;