rs549426099

Variant names:

• chr12-122341590-A-G
• rs549426099
• NM_001247997.2:c.1614T>C

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.1614T>C​(p.Pro538Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000152 in 1,613,810 control chromosomes in the GnomAD database, including 4 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.000085 (0 hom., cov: 31)
  • Exomes 𝑓: 0.00016 (4 hom.)
• Consequence: CLIP1 NM_001247997.2 synonymous
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.229
• Publications: 0 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=-0.8).
• BP6: Variant 12-122341590-A-G is Benign according to our data. Variant chr12-122341590-A-G is described in ClinVar as Likely_benign. ClinVar VariationId is 434782.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=0.229 with no splicing effect.
• BS2: High Homozygotes in GnomAdExome4 at 4 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.1614T>C	p.Pro538Pro	synonymous	Exon 11 of 26	NP_001234926.1	P30622-3
	CLIP1	NM_001389291.1		c.1476T>C	p.Pro492Pro	synonymous	Exon 9 of 25	NP_001376220.1
	CLIP1	NM_002956.3		c.1581T>C	p.Pro527Pro	synonymous	Exon 10 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.1614T>C	p.Pro538Pro	synonymous	Exon 11 of 26	ENSP00000479322.1	P30622-3
	CLIP1	ENST00000358808.6	TSL:1	c.1581T>C	p.Pro527Pro	synonymous	Exon 10 of 25	ENSP00000351665.2	P30622-1
	CLIP1	ENST00000537178.5	TSL:1	c.1476T>C	p.Pro492Pro	synonymous	Exon 9 of 24	ENSP00000445531.1	P30622-2

Frequencies

GnomAD3 genomes AF: 0.0000855 AC: 13 AN: 151990 Hom.: 0 Cov.: 31

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00270

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.000330 AC: 83 AN: 251268 AF XY: 0.000383

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: 0.00

Gnomad OTH exome AF: 0.000163

GnomAD4 exome AF: 0.000159 AC: 233 AN: 1461702 Hom.: 4 Cov.: 33 AF XY: 0.000209 AC XY: 152 AN XY: 727160

African (AFR) AF: 0.0000299 AC: 1 AN: 33480

American (AMR) AF: 0.00 AC: 0 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26136

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.00250 AC: 216 AN: 86256

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53244

Middle Eastern (MID) AF: 0.000347 AC: 2 AN: 5768

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1112000

Other (OTH) AF: 0.000232 AC: 14 AN: 60394

GnomAD4 genome AF: 0.0000855 AC: 13 AN: 152108 Hom.: 0 Cov.: 31 AF XY: 0.000121 AC XY: 9 AN XY: 74348

African (AFR) AF: 0.00 AC: 0 AN: 41478

American (AMR) AF: 0.00 AC: 0 AN: 15268

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5172

South Asian (SAS) AF: 0.00270 AC: 13 AN: 4818

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10584

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

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 68000

Other (OTH) AF: 0.00 AC: 0 AN: 2112

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.0000151

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, single submitter

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

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	7.0
DANN	Benign	0.64
PhyloP100		0.23
PromoterAI		-0.0076	Neutral
Mutation Taster		=100/0	polymorphism

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: rs549426099; hg19: chr12-122826137;