rs6957

Positions:

• chr19-41324701-T-C
• chr19-41324701-T-G

Variant summary

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

The NM_052848.3(CCDC97):​c.*1986T>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.214 in 152,034 control chromosomes in the GnomAD database, including 3,804 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 0.21 (3803 hom., cov: 32)
  • Exomes 𝑓: 0.11 (1 hom.)
• Consequence: CCDC97 NM_052848.3 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.835

Genes affected

CCDC97 (HGNC:28289): (coiled-coil domain containing 97)

TGFB1 (HGNC:11766): (transforming growth factor beta 1) This gene encodes a secreted ligand of the TGF-beta (transforming growth factor-beta) superfamily of proteins. Ligands of this family bind various TGF-beta receptors leading to recruitment and activation of SMAD family transcription factors that regulate gene expression. The encoded preproprotein is proteolytically processed to generate a latency-associated peptide (LAP) and a mature peptide, and is found in either a latent form composed of a mature peptide homodimer, a LAP homodimer, and a latent TGF-beta binding protein, or in an active form consisting solely of the mature peptide homodimer. The mature peptide may also form heterodimers with other TGFB family members. This encoded protein regulates cell proliferation, differentiation and growth, and can modulate expression and activation of other growth factors including interferon gamma and tumor necrosis factor alpha. This gene is frequently upregulated in tumor cells, and mutations in this gene result in Camurati-Engelmann disease. [provided by RefSeq, Aug 2016]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.334 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CCDC97	NM_052848.3	c.*1986T>C		3_prime_UTR_variant	5/5	ENST00000269967.4
CCDC97	NM_001346100.2	c.*1986T>C		3_prime_UTR_variant	5/5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CCDC97	ENST00000269967.4	c.*1986T>C		3_prime_UTR_variant	5/5	1	NM_052848.3	P1
TGFB1	ENST00000598758.5	n.302+7427A>G		intron_variant, non_coding_transcript_variant		5

Frequencies

GnomAD3 genomes AF: 0.214 AC: 32450 AN: 151880 Hom.: 3786 Cov.: 32

Gnomad AFR AF: 0.284

Gnomad AMI AF: 0.409

Gnomad AMR AF: 0.189

Gnomad ASJ AF: 0.202

Gnomad EAS AF: 0.348

Gnomad SAS AF: 0.194

Gnomad FIN AF: 0.152

Gnomad MID AF: 0.244

Gnomad NFE AF: 0.175

Gnomad OTH AF: 0.221

GnomAD4 exome AF: 0.111 AC: 4 AN: 36 Hom.: 1 Cov.: 0 AF XY: 0.200 AC XY: 4 AN XY: 20

Gnomad4 AFR exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.125

Gnomad4 OTH exome AF: 0.167

GnomAD4 genome AF: 0.214 AC: 32491 AN: 151998 Hom.: 3803 Cov.: 32 AF XY: 0.212 AC XY: 15766 AN XY: 74294

Gnomad4 AFR AF: 0.284

Gnomad4 AMR AF: 0.189

Gnomad4 ASJ AF: 0.202

Gnomad4 EAS AF: 0.348

Gnomad4 SAS AF: 0.193

Gnomad4 FIN AF: 0.152

Gnomad4 NFE AF: 0.175

Gnomad4 OTH AF: 0.220

Alfa AF: 0.182 Hom.: 3149

Bravo AF: 0.224

Asia WGS AF: 0.294 AC: 1023 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.85
DANN	Benign	0.69

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: rs6957; hg19: chr19-41830606;