rs2241718

Variant names:

• chr19-41323701-G-A
• rs2241718
• NM_052848.3:c.*986G>A

Your query was ambiguous. Multiple possible variants found:

• chr19-41323701-G-A
• chr19-41323701-G-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.*986G>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 155,382 control chromosomes in the GnomAD database, including 1,915 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 (1884 hom., cov: 32)
  • Exomes 𝑓: 0.13 (31 hom.)
• Consequence: CCDC97 NM_052848.3 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.111
• Publications: 38 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 -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.35).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.26 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CCDC97	NM_052848.3	c.*986G>A		3_prime_UTR_variant	Exon 5 of 5	ENST00000269967.4	NP_443080.1
CCDC97	NM_001346100.2	c.*986G>A		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.*986G>A		3_prime_UTR_variant	Exon 5 of 5	1	NM_052848.3	ENSP00000269967.2
TGFB1	ENST00000598758.5	n.302+8427C>T		intron_variant	Intron 2 of 3	5

Frequencies

GnomAD3 genomes AF: 0.147 AC: 22327 AN: 151844 Hom.: 1888 Cov.: 32

Gnomad AFR AF: 0.0850

Gnomad AMI AF: 0.412

Gnomad AMR AF: 0.141

Gnomad ASJ AF: 0.196

Gnomad EAS AF: 0.272

Gnomad SAS AF: 0.0996

Gnomad FIN AF: 0.150

Gnomad MID AF: 0.228

Gnomad NFE AF: 0.172

Gnomad OTH AF: 0.170

GnomAD4 exome AF: 0.127 AC: 433 AN: 3420 Hom.: 31 Cov.: 0 AF XY: 0.125 AC XY: 234 AN XY: 1872

African (AFR) AF: 0.0667 AC: 4 AN: 60

American (AMR) AF: 0.0417 AC: 1 AN: 24

Ashkenazi Jewish (ASJ) AF: 0.0789 AC: 6 AN: 76

East Asian (EAS) AF: 0.141 AC: 42 AN: 298

South Asian (SAS) AF: 0.0217 AC: 1 AN: 46

European-Finnish (FIN) AF: 0.144 AC: 113 AN: 784

Middle Eastern (MID) AF: 0.250 AC: 5 AN: 20

European-Non Finnish (NFE) AF: 0.122 AC: 237 AN: 1936

Other (OTH) AF: 0.136 AC: 24 AN: 176

GnomAD4 genome AF: 0.147 AC: 22319 AN: 151962 Hom.: 1884 Cov.: 32 AF XY: 0.144 AC XY: 10718 AN XY: 74270

African (AFR) AF: 0.0849 AC: 3520 AN: 41450

American (AMR) AF: 0.141 AC: 2150 AN: 15286

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

East Asian (EAS) AF: 0.272 AC: 1397 AN: 5144

South Asian (SAS) AF: 0.0997 AC: 480 AN: 4816

European-Finnish (FIN) AF: 0.150 AC: 1583 AN: 10558

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

European-Non Finnish (NFE) AF: 0.172 AC: 11716 AN: 67928

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

Alfa AF: 0.159 Hom.: 3590

Bravo AF: 0.148

Asia WGS AF: 0.193 AC: 672 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.35
CADD	Benign	12
DANN	Benign	0.86
PhyloP100		0.11
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

Other links and lift over

dbSNP: rs2241718; hg19: chr19-41829606;