rs229884

Positions:

• chr7-74307921-G-A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_003388.5(CLIP2):​c.-67-9559G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.596 in 152,052 control chromosomes in the GnomAD database, including 29,646 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 0.60 (29646 hom., cov: 32)
• Consequence: CLIP2 NM_003388.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.42

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=-0.96).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.732 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CLIP2	NM_003388.5	c.-67-9559G>A		intron_variant		ENST00000223398.11	NP_003379.4
CLIP2	NM_032421.3	c.-67-9559G>A		intron_variant			NP_115797.2
CLIP2	XM_047420800.1	c.-67-9559G>A		intron_variant			XP_047276756.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CLIP2	ENST00000223398.11	c.-67-9559G>A		intron_variant		5	NM_003388.5	ENSP00000223398	P3
CLIP2	ENST00000361545.9	c.-67-9559G>A		intron_variant		1		ENSP00000355151	A1

Frequencies

GnomAD3 genomes AF: 0.596 AC: 90536 AN: 151934 Hom.: 29642 Cov.: 32

Gnomad AFR AF: 0.307

Gnomad AMI AF: 0.838

Gnomad AMR AF: 0.624

Gnomad ASJ AF: 0.718

Gnomad EAS AF: 0.560

Gnomad SAS AF: 0.613

Gnomad FIN AF: 0.716

Gnomad MID AF: 0.715

Gnomad NFE AF: 0.737

Gnomad OTH AF: 0.616

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

GnomAD4 genome AF: 0.596 AC: 90558 AN: 152052 Hom.: 29646 Cov.: 32 AF XY: 0.595 AC XY: 44221 AN XY: 74326

Gnomad4 AFR AF: 0.307

Gnomad4 AMR AF: 0.624

Gnomad4 ASJ AF: 0.718

Gnomad4 EAS AF: 0.559

Gnomad4 SAS AF: 0.613

Gnomad4 FIN AF: 0.716

Gnomad4 NFE AF: 0.737

Gnomad4 OTH AF: 0.620

Alfa AF: 0.645 Hom.: 4416

Bravo AF: 0.571

Asia WGS AF: 0.538 AC: 1873 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	0.0020
DANN	Benign	0.46

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: rs229884; hg19: chr7-73722251;