2-29133701-G-T

Variant names:

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

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_024692.6(CLIP4):​c.414G>T​(p.Leu138Leu) variant causes a synonymous change. The variant allele was found at a frequency of 0.00000205 in 1,460,974 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: not found (cov: 32)
  • Exomes 𝑓: 0.0000021 (0 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.48).

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>T	p.Leu138Leu	synonymous	Exon 5 of 16	NP_078968.3
	CLIP4	NM_001287527.2		c.414G>T	p.Leu138Leu	synonymous	Exon 5 of 16	NP_001274456.1
	CLIP4	NM_001287528.2		c.414G>T	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>T	p.Leu138Leu	synonymous	Exon 5 of 16	ENSP00000327009.5
	CLIP4	ENST00000687506.1		c.414G>T	p.Leu138Leu	synonymous	Exon 5 of 16	ENSP00000509486.1
	CLIP4	ENST00000404424.5	TSL:5	c.414G>T	p.Leu138Leu	synonymous	Exon 5 of 16	ENSP00000385594.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD2 exomes AF: 0.00000400 AC: 1 AN: 250236 AF XY: 0.00000739

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00000883

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000205 AC: 3 AN: 1460974 Hom.: 0 Cov.: 32 AF XY: 0.00000413 AC XY: 3 AN XY: 726774

African (AFR) AF: 0.00 AC: 0 AN: 33434

American (AMR) AF: 0.00 AC: 0 AN: 44484

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26102

East Asian (EAS) AF: 0.00 AC: 0 AN: 39670

South Asian (SAS) AF: 0.0000232 AC: 2 AN: 86064

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53394

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5760

European-Non Finnish (NFE) AF: 9.00e-7 AC: 1 AN: 1111700

Other (OTH) AF: 0.00 AC: 0 AN: 60366

GnomAD4 genome Cov.: 32

EpiCase AF: 0.00

EpiControl AF: 0.0000593

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.48
CADD	Benign	7.7
DANN	Benign	0.62
PhyloP100		3.9
Mutation Taster		=93/7	polymorphism

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;