NM_024692.6:c.414G>C

Variant names:

• chr2-29133701-G-C
• rs17749904
• NM_024692.6:c.414G>C

Variant summary

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

The NM_024692.6(CLIP4):​c.414G>C​(p.Leu138Leu) variant causes a synonymous change. The variant allele was found at a frequency of 0.206 in 1,612,820 control chromosomes in the GnomAD database, including 36,902 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 0.17 (2616 hom., cov: 32)
  • Exomes 𝑓: 0.21 (34286 hom.)
• Consequence: CLIP4 NM_024692.6 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.93

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=-0.48).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.223 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CLIP4	NM_024692.6	c.414G>C	p.Leu138Leu	synonymous_variant	Exon 5 of 16	ENST00000320081.10	NP_078968.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CLIP4	ENST00000320081.10	c.414G>C	p.Leu138Leu	synonymous_variant	Exon 5 of 16	1	NM_024692.6	ENSP00000327009.5

Frequencies

GnomAD3 genomes AF: 0.170 AC: 25912 AN: 152042 Hom.: 2614 Cov.: 32

Gnomad AFR AF: 0.0849

Gnomad AMI AF: 0.0746

Gnomad AMR AF: 0.130

Gnomad ASJ AF: 0.301

Gnomad EAS AF: 0.0100

Gnomad SAS AF: 0.233

Gnomad FIN AF: 0.226

Gnomad MID AF: 0.222

Gnomad NFE AF: 0.226

Gnomad OTH AF: 0.155

GnomAD3 exomes AF: 0.191 AC: 47680 AN: 250236 Hom.: 5352 AF XY: 0.199 AC XY: 26905 AN XY: 135248

Gnomad AFR exome AF: 0.0853

Gnomad AMR exome AF: 0.115

Gnomad ASJ exome AF: 0.296

Gnomad EAS exome AF: 0.00822

Gnomad SAS exome AF: 0.250

Gnomad FIN exome AF: 0.228

Gnomad NFE exome AF: 0.225

Gnomad OTH exome AF: 0.194

GnomAD4 exome AF: 0.210 AC: 306314 AN: 1460660 Hom.: 34286 Cov.: 32 AF XY: 0.212 AC XY: 154014 AN XY: 726624

Gnomad4 AFR exome AF: 0.0828

Gnomad4 AMR exome AF: 0.117

Gnomad4 ASJ exome AF: 0.289

Gnomad4 EAS exome AF: 0.0132

Gnomad4 SAS exome AF: 0.248

Gnomad4 FIN exome AF: 0.225

Gnomad4 NFE exome AF: 0.219

Gnomad4 OTH exome AF: 0.200

GnomAD4 genome AF: 0.170 AC: 25916 AN: 152160 Hom.: 2616 Cov.: 32 AF XY: 0.169 AC XY: 12555 AN XY: 74382

Gnomad4 AFR AF: 0.0848

Gnomad4 AMR AF: 0.130

Gnomad4 ASJ AF: 0.301

Gnomad4 EAS AF: 0.0100

Gnomad4 SAS AF: 0.234

Gnomad4 FIN AF: 0.226

Gnomad4 NFE AF: 0.226

Gnomad4 OTH AF: 0.153

Alfa AF: 0.220 Hom.: 1265

Bravo AF: 0.154

Asia WGS AF: 0.0960 AC: 334 AN: 3478

EpiCase AF: 0.218

EpiControl AF: 0.214

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.48
CADD	Benign	7.5
DANN	Benign	0.62

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: rs17749904; hg19: chr2-29356567;