7-74366482-C-G

Variant names:

• chr7-74366482-C-G
• rs512023
• NM_003388.5:c.1380+2167C>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_003388.5(CLIP2):​c.1380+2167C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.335 in 152,170 control chromosomes in the GnomAD database, including 9,764 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.33 (9764 hom., cov: 32)
• Consequence: CLIP2 NM_003388.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.898
• Publications: 7 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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.95).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.432 is higher than 0.05.

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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CLIP2	NM_003388.5	MANE Select	c.1380+2167C>G		intron	N/A	NP_003379.4
	CLIP2	NM_032421.3		c.1380+2167C>G		intron	N/A	NP_115797.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CLIP2	ENST00000223398.11	TSL:5 MANE Select	c.1380+2167C>G		intron	N/A	ENSP00000223398.6
	CLIP2	ENST00000361545.9	TSL:1	c.1380+2167C>G		intron	N/A	ENSP00000355151.5
	CLIP2	ENST00000884300.1		c.1482+2167C>G		intron	N/A	ENSP00000554359.1

Frequencies

GnomAD3 genomes AF: 0.335 AC: 50889 AN: 152052 Hom.: 9753 Cov.: 32

Gnomad AFR AF: 0.137

Gnomad AMI AF: 0.488

Gnomad AMR AF: 0.390

Gnomad ASJ AF: 0.445

Gnomad EAS AF: 0.379

Gnomad SAS AF: 0.448

Gnomad FIN AF: 0.355

Gnomad MID AF: 0.472

Gnomad NFE AF: 0.418

Gnomad OTH AF: 0.384

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.335 AC: 50906 AN: 152170 Hom.: 9764 Cov.: 32 AF XY: 0.336 AC XY: 24975 AN XY: 74404

African (AFR) AF: 0.137 AC: 5690 AN: 41540

American (AMR) AF: 0.391 AC: 5961 AN: 15264

Ashkenazi Jewish (ASJ) AF: 0.445 AC: 1544 AN: 3472

East Asian (EAS) AF: 0.378 AC: 1956 AN: 5174

South Asian (SAS) AF: 0.447 AC: 2160 AN: 4828

European-Finnish (FIN) AF: 0.355 AC: 3762 AN: 10596

Middle Eastern (MID) AF: 0.476 AC: 140 AN: 294

European-Non Finnish (NFE) AF: 0.418 AC: 28423 AN: 67980

Other (OTH) AF: 0.391 AC: 827 AN: 2114

Alfa AF: 0.365 Hom.: 1493

Bravo AF: 0.327

Asia WGS AF: 0.412 AC: 1434 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	0.27
DANN	Benign	0.37
PhyloP100		-0.90
Mutation Taster		=100/0	polymorphism (auto)

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: rs512023; hg19: chr7-73780812;