10-32456325-A-G

Variant names:

• chr10-32456325-A-G
• rs746235004
• NM_001395015.1:c.447A>G

Variant summary

Our verdict is Likely benign. The variant received -3 ACMG points: 2P and 5B. PM2 BP4_Strong BP7

The NM_001395015.1(CCDC7):​c.447A>G​(p.Glu149Glu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000705 in 1,419,206 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: 7.0e-7 (0 hom.)
• Consequence: CCDC7 NM_001395015.1 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.959
• Publications: 0 publications found

Genes affected

CCDC7 (HGNC:26533): (coiled-coil domain containing 7)

CCDC7 Gene-Disease associations (from GenCC):

• Tourette syndrome

  Inheritance: Unknown Classification: NO_KNOWN Submitted by: Labcorp Genetics (formerly Invitae)

ACMG classification

Our verdict: Likely_benign. The variant received -3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.56).
• BP7: Synonymous conserved (PhyloP=0.959 with no splicing effect.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001395015.1. 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
	CCDC7	NM_001395015.1	MANE Select	c.447A>G	p.Glu149Glu	synonymous	Exon 4 of 44	NP_001381944.1	Q96M83-1
	CCDC7	NM_001321115.2		c.447A>G	p.Glu149Glu	synonymous	Exon 4 of 44	NP_001308044.1	Q96M83-1
	CCDC7	NM_001395233.1		c.447A>G	p.Glu149Glu	synonymous	Exon 4 of 15	NP_001382162.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CCDC7	ENST00000639629.2	TSL:5 MANE Select	c.447A>G	p.Glu149Glu	synonymous	Exon 4 of 44	ENSP00000491655.1	Q96M83-1
	CCDC7	ENST00000277657.12	TSL:1	c.447A>G	p.Glu149Glu	synonymous	Exon 4 of 18	ENSP00000277657.6	Q96M83-3
	CCDC7	ENST00000362006.11	TSL:1	c.447A>G	p.Glu149Glu	synonymous	Exon 4 of 18	ENSP00000355078.5	Q96M83-3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD2 exomes AF: 0.00000403 AC: 1 AN: 248430 AF XY: 0.00000745

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: 0.00000886

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 7.05e-7 AC: 1 AN: 1419206 Hom.: 0 Cov.: 30 AF XY: 0.00000142 AC XY: 1 AN XY: 702658

African (AFR) AF: 0.00 AC: 0 AN: 33040

American (AMR) AF: 0.00 AC: 0 AN: 44046

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 24976

East Asian (EAS) AF: 0.00 AC: 0 AN: 39090

South Asian (SAS) AF: 0.00 AC: 0 AN: 79856

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 51998

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5574

European-Non Finnish (NFE) AF: 9.24e-7 AC: 1 AN: 1082446

Other (OTH) AF: 0.00 AC: 0 AN: 58180

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.56
CADD	Benign	2.6
DANN	Benign	0.43
PhyloP100		0.96

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs746235004; hg19: chr10-32745253;