rs2241719

chr19-41323676-T-Achr19-41323676-T-C

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_Moderate BA1

The NM_052848.3(CCDC97):c.*961T>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.146 in 155,252 control chromosomes in the GnomAD database, including 1,916 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 0.15 (1886 hom., cov: 32)
  • Exomes 𝑓: 0.12 (30 hom.)
• Consequence: CCDC97 NM_052848.3 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0790

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 -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.41).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.263 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CCDC97	NM_052848.3	c.*961T>A		3_prime_UTR_variant	5/5	ENST00000269967.4
CCDC97	NM_001346100.2	c.*961T>A		3_prime_UTR_variant	5/5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CCDC97	ENST00000269967.4	c.*961T>A		3_prime_UTR_variant	5/5	1	NM_052848.3	P1
TGFB1	ENST00000598758.5	n.302+8452A>T		intron_variant, non_coding_transcript_variant		5

Frequencies

GnomAD3 genomes AF: 0.147 AC: 22338 AN: 151860 Hom.: 1890 Cov.: 32

Gnomad AFR AF: 0.0850

Gnomad AMI AF: 0.407

Gnomad AMR AF: 0.141

Gnomad ASJ AF: 0.196

Gnomad EAS AF: 0.275

Gnomad SAS AF: 0.0999

Gnomad FIN AF: 0.150

Gnomad MID AF: 0.228

Gnomad NFE AF: 0.172

Gnomad OTH AF: 0.170

GnomAD4 exome AF: 0.121 AC: 397 AN: 3274 Hom.: 30 Cov.: 0 AF XY: 0.117 AC XY: 217 AN XY: 1856

Gnomad4 AFR exome AF: 0.0577

Gnomad4 AMR exome AF: 0.0769

Gnomad4 ASJ exome AF: 0.0606

Gnomad4 EAS exome AF: 0.124

Gnomad4 SAS exome AF: 0.0862

Gnomad4 FIN exome AF: 0.135

Gnomad4 NFE exome AF: 0.118

Gnomad4 OTH exome AF: 0.154

GnomAD4 genome AF: 0.147 AC: 22330 AN: 151978 Hom.: 1886 Cov.: 32 AF XY: 0.144 AC XY: 10724 AN XY: 74280

Gnomad4 AFR AF: 0.0849

Gnomad4 AMR AF: 0.141

Gnomad4 ASJ AF: 0.196

Gnomad4 EAS AF: 0.275

Gnomad4 SAS AF: 0.100

Gnomad4 FIN AF: 0.150

Gnomad4 NFE AF: 0.173

Gnomad4 OTH AF: 0.170

Alfa AF: 0.152 Hom.: 241

Bravo AF: 0.148

Asia WGS AF: 0.193 AC: 673 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.41
Cadd	Benign	14
Dann	Benign	0.91
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.2

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: rs2241719; hg19: chr19-41829581; COSMIC: COSV54189382; COSMIC: COSV54189382;