7-74366482-C-G

Position:

• chr7-74366482-C-G

Variant summary

Our verdict is Benign. Variant got -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

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

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CLIP2	NM_003388.5	c.1380+2167C>G		intron_variant		ENST00000223398.11	NP_003379.4
CLIP2	NM_032421.3	c.1380+2167C>G		intron_variant			NP_115797.2
CLIP2	XM_047420800.1	c.1380+2167C>G		intron_variant			XP_047276756.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CLIP2	ENST00000223398.11	c.1380+2167C>G		intron_variant		5	NM_003388.5	ENSP00000223398.6
CLIP2	ENST00000361545.9	c.1380+2167C>G		intron_variant		1		ENSP00000355151.5

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

Gnomad4 AFR AF: 0.137

Gnomad4 AMR AF: 0.391

Gnomad4 ASJ AF: 0.445

Gnomad4 EAS AF: 0.378

Gnomad4 SAS AF: 0.447

Gnomad4 FIN AF: 0.355

Gnomad4 NFE AF: 0.418

Gnomad4 OTH AF: 0.391

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 v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	0.27
DANN	Benign	0.37

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

Publications

LitVar

Other links and lift over

dbSNP: rs512023; hg19: chr7-73780812;