rs2305450

Positions:

• chr2-29160508-G-A
• chr2-29160508-G-T

Variant summary

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

The NM_024692.6(CLIP4):​c.1534+41G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.899 in 1,605,518 control chromosomes in the GnomAD database, including 650,446 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 0.88 (59630 hom., cov: 32)
  • Exomes 𝑓: 0.90 (590816 hom.)
• Consequence: CLIP4 NM_024692.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.102

Genes affected

CLIP4 (HGNC:26108): (CAP-Gly domain containing linker protein family member 4) Predicted to enable microtubule plus-end binding activity. Predicted to be involved in cytoplasmic microtubule organization. Located in intracellular membrane-bounded organelle. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.94).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.906 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CLIP4	NM_024692.6	c.1534+41G>A		intron_variant		ENST00000320081.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CLIP4	ENST00000320081.10	c.1534+41G>A		intron_variant		1	NM_024692.6	P1

Frequencies

GnomAD3 genomes AF: 0.884 AC: 134475 AN: 152128 Hom.: 59578 Cov.: 32

Gnomad AFR AF: 0.827

Gnomad AMI AF: 0.838

Gnomad AMR AF: 0.909

Gnomad ASJ AF: 0.878

Gnomad EAS AF: 0.868

Gnomad SAS AF: 0.837

Gnomad FIN AF: 0.931

Gnomad MID AF: 0.826

Gnomad NFE AF: 0.912

Gnomad OTH AF: 0.880

GnomAD3 exomes AF: 0.896 AC: 220732 AN: 246486 Hom.: 99015 AF XY: 0.892 AC XY: 118670 AN XY: 133002

Gnomad AFR exome AF: 0.828

Gnomad AMR exome AF: 0.940

Gnomad ASJ exome AF: 0.884

Gnomad EAS exome AF: 0.870

Gnomad SAS exome AF: 0.824

Gnomad FIN exome AF: 0.930

Gnomad NFE exome AF: 0.909

Gnomad OTH exome AF: 0.897

GnomAD4 exome AF: 0.901 AC: 1309472 AN: 1453272 Hom.: 590816 Cov.: 30 AF XY: 0.899 AC XY: 649166 AN XY: 722252

Gnomad4 AFR exome AF: 0.827

Gnomad4 AMR exome AF: 0.937

Gnomad4 ASJ exome AF: 0.884

Gnomad4 EAS exome AF: 0.842

Gnomad4 SAS exome AF: 0.826

Gnomad4 FIN exome AF: 0.927

Gnomad4 NFE exome AF: 0.910

Gnomad4 OTH exome AF: 0.887

GnomAD4 genome AF: 0.884 AC: 134584 AN: 152246 Hom.: 59630 Cov.: 32 AF XY: 0.885 AC XY: 65860 AN XY: 74438

Gnomad4 AFR AF: 0.827

Gnomad4 AMR AF: 0.909

Gnomad4 ASJ AF: 0.878

Gnomad4 EAS AF: 0.868

Gnomad4 SAS AF: 0.836

Gnomad4 FIN AF: 0.931

Gnomad4 NFE AF: 0.912

Gnomad4 OTH AF: 0.881

Alfa AF: 0.900 Hom.: 42842

Bravo AF: 0.879

Asia WGS AF: 0.867 AC: 3016 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	0.24
DANN	Benign	0.30

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: rs2305450; hg19: chr2-29383374;