2-29133701-G-C

Variant names:

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

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 13 publications found

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

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_024692.6. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CLIP4	NM_024692.6	MANE Select	c.414G>C	p.Leu138Leu	synonymous	Exon 5 of 16	NP_078968.3
	CLIP4	NM_001287527.2		c.414G>C	p.Leu138Leu	synonymous	Exon 5 of 16	NP_001274456.1
	CLIP4	NM_001287528.2		c.414G>C	p.Leu138Leu	synonymous	Exon 5 of 15	NP_001274457.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CLIP4	ENST00000320081.10	TSL:1 MANE Select	c.414G>C	p.Leu138Leu	synonymous	Exon 5 of 16	ENSP00000327009.5
	CLIP4	ENST00000687506.1		c.414G>C	p.Leu138Leu	synonymous	Exon 5 of 16	ENSP00000509486.1
	CLIP4	ENST00000404424.5	TSL:5	c.414G>C	p.Leu138Leu	synonymous	Exon 5 of 16	ENSP00000385594.1

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

GnomAD2 exomes AF: 0.191 AC: 47680 AN: 250236 AF XY: 0.199

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 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

African (AFR) AF: 0.0828 AC: 2769 AN: 33430

American (AMR) AF: 0.117 AC: 5197 AN: 44466

Ashkenazi Jewish (ASJ) AF: 0.289 AC: 7549 AN: 26092

East Asian (EAS) AF: 0.0132 AC: 524 AN: 39668

South Asian (SAS) AF: 0.248 AC: 21371 AN: 86014

European-Finnish (FIN) AF: 0.225 AC: 12035 AN: 53388

Middle Eastern (MID) AF: 0.239 AC: 1376 AN: 5758

European-Non Finnish (NFE) AF: 0.219 AC: 243397 AN: 1111494

Other (OTH) AF: 0.200 AC: 12096 AN: 60350

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

African (AFR) AF: 0.0848 AC: 3520 AN: 41518

American (AMR) AF: 0.130 AC: 1983 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.301 AC: 1045 AN: 3470

East Asian (EAS) AF: 0.0100 AC: 52 AN: 5186

South Asian (SAS) AF: 0.234 AC: 1130 AN: 4822

European-Finnish (FIN) AF: 0.226 AC: 2388 AN: 10578

Middle Eastern (MID) AF: 0.218 AC: 64 AN: 294

European-Non Finnish (NFE) AF: 0.226 AC: 15344 AN: 67996

Other (OTH) AF: 0.153 AC: 322 AN: 2110

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 v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.48
CADD	Benign	7.5
DANN	Benign	0.62
PhyloP100		3.9
Mutation Taster		=93/7	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: rs17749904; hg19: chr2-29356567;