7-74338482-C-T

Variant names:

• chr7-74338482-C-T
• rs112253688
• NM_003388.5:c.156C>T

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BS1 BS2

The NM_003388.5(CLIP2):​c.156C>T​(p.Ser52Ser) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00182 in 1,612,716 control chromosomes in the GnomAD database, including 16 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0054 (3 hom., cov: 32)
  • Exomes 𝑓: 0.0014 (13 hom.)
• Consequence: CLIP2 NM_003388.5 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.304
• Publications: 1 publications found

Genes affected

CLIP2 (HGNC:2586): (CAP-Gly domain containing linker protein 2) The protein encoded by this gene belongs to the family of cytoplasmic linker proteins, which have been proposed to mediate the interaction between specific membranous organelles and microtubules. This protein was found to associate with both microtubules and an organelle called the dendritic lamellar body. This gene is hemizygously deleted in Williams syndrome, a multisystem developmental disorder caused by the deletion of contiguous genes at 7q11.23. Alternative splicing of this gene generates 2 transcript variants. [provided by RefSeq, Jul 2008]

ACMG classification

Our verdict: Benign. The variant received -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.63).
• BP6: Variant 7-74338482-C-T is Benign according to our data. Variant chr7-74338482-C-T is described in ClinVar as Benign. ClinVar VariationId is 790594.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=0.304 with no splicing effect.
• BS1: Variant frequency is greater than expected in population afr. GnomAdExome4 allele frequency = 0.00145 (2114/1460434) while in subpopulation AFR AF = 0.0166 (556/33454). AF 95% confidence interval is 0.0155. There are 13 homozygotes in GnomAdExome4. There are 946 alleles in the male GnomAdExome4 subpopulation. Median coverage is 33. This position passed quality control check.
• BS2: High AC in GnomAd4 at 815 AD gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_003388.5. 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
	CLIP2	NM_003388.5	MANE Select	c.156C>T	p.Ser52Ser	synonymous	Exon 3 of 17	NP_003379.4
	CLIP2	NM_032421.3		c.156C>T	p.Ser52Ser	synonymous	Exon 3 of 16	NP_115797.2	Q9UDT6-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CLIP2	ENST00000223398.11	TSL:5 MANE Select	c.156C>T	p.Ser52Ser	synonymous	Exon 3 of 17	ENSP00000223398.6	Q9UDT6-1
	CLIP2	ENST00000361545.9	TSL:1	c.156C>T	p.Ser52Ser	synonymous	Exon 3 of 16	ENSP00000355151.5	Q9UDT6-2
	CLIP2	ENST00000884300.1		c.156C>T	p.Ser52Ser	synonymous	Exon 3 of 18	ENSP00000554359.1

Frequencies

GnomAD3 genomes AF: 0.00523 AC: 796 AN: 152164 Hom.: 1 Cov.: 32

Gnomad AFR AF: 0.0155

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00373

Gnomad ASJ AF: 0.000577

Gnomad EAS AF: 0.000193

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00115

Gnomad OTH AF: 0.00764

GnomAD2 exomes AF: 0.00221 AC: 542 AN: 245628 AF XY: 0.00169

Gnomad AFR exome AF: 0.0163

Gnomad AMR exome AF: 0.00370

Gnomad ASJ exome AF: 0.000706

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00115

Gnomad OTH exome AF: 0.00383

GnomAD4 exome AF: 0.00145 AC: 2114 AN: 1460434 Hom.: 13 Cov.: 33 AF XY: 0.00130 AC XY: 946 AN XY: 726482

African (AFR) AF: 0.0166 AC: 556 AN: 33454

American (AMR) AF: 0.00412 AC: 184 AN: 44626

Ashkenazi Jewish (ASJ) AF: 0.000536 AC: 14 AN: 26122

East Asian (EAS) AF: 0.00 AC: 0 AN: 39688

South Asian (SAS) AF: 0.000267 AC: 23 AN: 86146

European-Finnish (FIN) AF: 0.0000190 AC: 1 AN: 52602

Middle Eastern (MID) AF: 0.0116 AC: 66 AN: 5708

European-Non Finnish (NFE) AF: 0.000917 AC: 1019 AN: 1111756

Other (OTH) AF: 0.00416 AC: 251 AN: 60332

GnomAD4 genome AF: 0.00535 AC: 815 AN: 152282 Hom.: 3 Cov.: 32 AF XY: 0.00525 AC XY: 391 AN XY: 74454

African (AFR) AF: 0.0159 AC: 661 AN: 41568

American (AMR) AF: 0.00373 AC: 57 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.000577 AC: 2 AN: 3466

East Asian (EAS) AF: 0.000193 AC: 1 AN: 5174

South Asian (SAS) AF: 0.00 AC: 0 AN: 4820

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10618

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

European-Non Finnish (NFE) AF: 0.00115 AC: 78 AN: 68022

Other (OTH) AF: 0.00756 AC: 16 AN: 2116

Alfa AF: 0.00317 Hom.: 0

Bravo AF: 0.00626

Asia WGS AF: 0.00577 AC: 20 AN: 3478

EpiCase AF: 0.00185

EpiControl AF: 0.00160

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.63
CADD	Benign	3.4
DANN	Benign	0.66
PhyloP100		0.30
Mutation Taster		=100/0	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs112253688; hg19: chr7-73752812;