rs2241719

Variant names:

• chr19-41323676-T-A
• rs2241719
• NM_052848.3:c.*961T>A

Your query was ambiguous. Multiple possible variants found:

• chr19-41323676-T-A
• chr19-41323676-T-C

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 14 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, PanelApp Australia, G2P, Ambry Genetics, Labcorp Genetics (formerly Invitae), Genomics England PanelApp
• inflammatory bowel disease, immunodeficiency, and encephalopathy

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

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_052848.3. 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
	CCDC97	NM_052848.3	MANE Select	c.*961T>A		3_prime_UTR	Exon 5 of 5	NP_443080.1	Q96F63
	CCDC97	NM_001346100.2		c.*961T>A		3_prime_UTR	Exon 5 of 5	NP_001333029.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CCDC97	ENST00000269967.4	TSL:1 MANE Select	c.*961T>A		3_prime_UTR	Exon 5 of 5	ENSP00000269967.2	Q96F63
	CCDC97	ENST00000886246.1		c.*961T>A		3_prime_UTR	Exon 6 of 6	ENSP00000556305.1
	TGFB1	ENST00000598758.5	TSL:5	n.302+8452A>T		intron	N/A

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

African (AFR) AF: 0.0577 AC: 3 AN: 52

American (AMR) AF: 0.0769 AC: 2 AN: 26

Ashkenazi Jewish (ASJ) AF: 0.0606 AC: 4 AN: 66

East Asian (EAS) AF: 0.124 AC: 27 AN: 218

South Asian (SAS) AF: 0.0862 AC: 5 AN: 58

European-Finnish (FIN) AF: 0.135 AC: 104 AN: 772

Middle Eastern (MID) AF: 0.188 AC: 3 AN: 16

European-Non Finnish (NFE) AF: 0.118 AC: 225 AN: 1910

Other (OTH) AF: 0.154 AC: 24 AN: 156

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

African (AFR) AF: 0.0849 AC: 3519 AN: 41472

American (AMR) AF: 0.141 AC: 2149 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.196 AC: 679 AN: 3472

East Asian (EAS) AF: 0.275 AC: 1411 AN: 5130

South Asian (SAS) AF: 0.100 AC: 482 AN: 4820

European-Finnish (FIN) AF: 0.150 AC: 1583 AN: 10578

Middle Eastern (MID) AF: 0.214 AC: 63 AN: 294

European-Non Finnish (NFE) AF: 0.173 AC: 11717 AN: 67922

Other (OTH) AF: 0.170 AC: 357 AN: 2106

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 v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.41
CADD	Benign	14
DANN	Benign	0.91
PhyloP100		0.079
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.2
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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs2241719;

hg19: chr19-41829581;

COSMIC: COSV54189382;

COSMIC: COSV54189382;