rs6957

Variant names:

• chr19-41324701-T-C
• rs6957
• NM_052848.3:c.*1986T>C

Your query was ambiguous. Multiple possible variants found:

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

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 36 publications found

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]

TGFB1 Gene-Disease associations (from GenCC):

• Camurati-Engelmann disease

  Inheritance: AD Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Orphanet, Genomics England PanelApp, Labcorp Genetics (formerly Invitae), G2P, Ambry Genetics
• inflammatory bowel disease, immunodeficiency, and encephalopathy

  Inheritance: AR Classification: STRONG, SUPPORTIVE, LIMITED Submitted by: Orphanet, Labcorp Genetics (formerly Invitae), Ambry Genetics
• cystic fibrosis

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
CCDC97	NM_052848.3	c.*1986T>C		3_prime_UTR_variant	Exon 5 of 5	ENST00000269967.4	NP_443080.1
CCDC97	NM_001346100.2	c.*1986T>C		3_prime_UTR_variant	Exon 5 of 5		NP_001333029.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CCDC97	ENST00000269967.4	c.*1986T>C		3_prime_UTR_variant	Exon 5 of 5	1	NM_052848.3	ENSP00000269967.2
TGFB1	ENST00000598758.5	n.302+7427A>G		intron_variant	Intron 2 of 3	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

African (AFR) AF: 0.00 AC: 0 AN: 2

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AF: 0.00 AC: 0 AN: 2

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 2

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.125 AC: 3 AN: 24

Other (OTH) AF: 0.167 AC: 1 AN: 6

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

African (AFR) AF: 0.284 AC: 11768 AN: 41418

American (AMR) AF: 0.189 AC: 2881 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.202 AC: 701 AN: 3472

East Asian (EAS) AF: 0.348 AC: 1795 AN: 5164

South Asian (SAS) AF: 0.193 AC: 933 AN: 4822

European-Finnish (FIN) AF: 0.152 AC: 1612 AN: 10576

Middle Eastern (MID) AF: 0.231 AC: 68 AN: 294

European-Non Finnish (NFE) AF: 0.175 AC: 11896 AN: 67946

Other (OTH) AF: 0.220 AC: 465 AN: 2114

Alfa AF: 0.188 Hom.: 5114

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
PhyloP100		-0.83
Mutation Taster		=100/0	polymorphism (auto)

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: rs6957; hg19: chr19-41830606;