7-74370840-G-C

Variant names:

• chr7-74370840-G-C
• rs2528994
• NM_003388.5:c.1381-2092G>C

Variant summary

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

The NM_003388.5(CLIP2):​c.1381-2092G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.37 in 151,534 control chromosomes in the GnomAD database, including 11,241 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 0.37 (11241 hom., cov: 29)
• Consequence: CLIP2 NM_003388.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.958
• Publications: 4 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=-1.03).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.441 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CLIP2	NM_003388.5	MANE Select	c.1381-2092G>C		intron	N/A	NP_003379.4
	CLIP2	NM_032421.3		c.1381-5047G>C		intron	N/A	NP_115797.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CLIP2	ENST00000223398.11	TSL:5 MANE Select	c.1381-2092G>C		intron	N/A	ENSP00000223398.6
	CLIP2	ENST00000361545.9	TSL:1	c.1381-5047G>C		intron	N/A	ENSP00000355151.5
	CLIP2	ENST00000884300.1		c.1483-2092G>C		intron	N/A	ENSP00000554359.1

Frequencies

GnomAD3 genomes AF: 0.370 AC: 55994 AN: 151416 Hom.: 11227 Cov.: 29

Gnomad AFR AF: 0.208

Gnomad AMI AF: 0.494

Gnomad AMR AF: 0.403

Gnomad ASJ AF: 0.456

Gnomad EAS AF: 0.388

Gnomad SAS AF: 0.456

Gnomad FIN AF: 0.371

Gnomad MID AF: 0.475

Gnomad NFE AF: 0.445

Gnomad OTH AF: 0.415

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

GnomAD4 genome AF: 0.370 AC: 56025 AN: 151534 Hom.: 11241 Cov.: 29 AF XY: 0.369 AC XY: 27312 AN XY: 74026

African (AFR) AF: 0.207 AC: 8559 AN: 41278

American (AMR) AF: 0.403 AC: 6116 AN: 15168

Ashkenazi Jewish (ASJ) AF: 0.456 AC: 1579 AN: 3464

East Asian (EAS) AF: 0.387 AC: 1994 AN: 5148

South Asian (SAS) AF: 0.456 AC: 2183 AN: 4792

European-Finnish (FIN) AF: 0.371 AC: 3889 AN: 10470

Middle Eastern (MID) AF: 0.480 AC: 141 AN: 294

European-Non Finnish (NFE) AF: 0.445 AC: 30228 AN: 67908

Other (OTH) AF: 0.422 AC: 887 AN: 2104

Alfa AF: 0.289 Hom.: 876

Bravo AF: 0.363

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.41
DANN	Benign	0.56
PhyloP100		-0.96
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: rs2528994; hg19: chr7-73785170;