rs12244832

Positions:

• chr10-32583192-C-T

Variant summary

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

The NM_001395015.1(CCDC7):​c.1613C>T​(p.Thr538Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.104 in 1,231,126 control chromosomes in the GnomAD database, including 7,486 homozygotes. In-silico tool predicts a benign outcome for this variant. 7/10 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.11 (1167 hom., cov: 31)
  • Exomes 𝑓: 0.10 (6319 hom.)
• Consequence: CCDC7 NM_001395015.1 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.813

Genes affected

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

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0016908348).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.256 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CCDC7	NM_001395015.1	c.1613C>T	p.Thr538Ile	missense_variant	18/44	ENST00000639629.2	NP_001381944.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CCDC7	ENST00000639629.2	c.1613C>T	p.Thr538Ile	missense_variant	18/44	5	NM_001395015.1	ENSP00000491655	A2
CCDC7	ENST00000639290.1	n.348C>T		non_coding_transcript_exon_variant	4/23	1
CCDC7	ENST00000302316.12	c.56+15301C>T		intron_variant, NMD_transcript_variant		1		ENSP00000303710
CCDC7	ENST00000375025.10	c.*138C>T		3_prime_UTR_variant, NMD_transcript_variant	2/23	2		ENSP00000364165

Frequencies

GnomAD3 genomes AF: 0.113 AC: 17160 AN: 151926 Hom.: 1165 Cov.: 31

Gnomad AFR AF: 0.0875

Gnomad AMI AF: 0.163

Gnomad AMR AF: 0.205

Gnomad ASJ AF: 0.0914

Gnomad EAS AF: 0.169

Gnomad SAS AF: 0.268

Gnomad FIN AF: 0.114

Gnomad MID AF: 0.117

Gnomad NFE AF: 0.0931

Gnomad OTH AF: 0.105

GnomAD4 exome AF: 0.103 AC: 111082 AN: 1079084 Hom.: 6319 Cov.: 31 AF XY: 0.103 AC XY: 52588 AN XY: 509430

Gnomad4 AFR exome AF: 0.0893

Gnomad4 AMR exome AF: 0.220

Gnomad4 ASJ exome AF: 0.0875

Gnomad4 EAS exome AF: 0.191

Gnomad4 SAS exome AF: 0.262

Gnomad4 FIN exome AF: 0.113

Gnomad4 NFE exome AF: 0.0953

Gnomad4 OTH exome AF: 0.121

GnomAD4 genome AF: 0.113 AC: 17175 AN: 152042 Hom.: 1167 Cov.: 31 AF XY: 0.118 AC XY: 8785 AN XY: 74328

Gnomad4 AFR AF: 0.0873

Gnomad4 AMR AF: 0.205

Gnomad4 ASJ AF: 0.0914

Gnomad4 EAS AF: 0.169

Gnomad4 SAS AF: 0.268

Gnomad4 FIN AF: 0.114

Gnomad4 NFE AF: 0.0932

Gnomad4 OTH AF: 0.105

Alfa AF: 0.104 Hom.: 489

Bravo AF: 0.116

TwinsUK AF: 0.0893 AC: 331

ALSPAC AF: 0.104 AC: 399

Asia WGS AF: 0.223 AC: 776 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.17
BayesDel_noAF	Benign	-0.83
CADD	Benign	0.59
DANN	Benign	0.85
FATHMM_MKL	Benign	0.037	N
LIST_S2	Benign	0.49	T
MetaRNN	Benign	0.0017	T
MutationTaster	Benign	1.0	P;P;P
GERP RS		-2.6
Varity_R		0.031
gMVP		0.011

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs12244832; hg19: chr10-32872120; COSMIC: COSV56554906;