rs11709673

Positions:

• chr3-14671799-A-G

Variant summary

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

The NM_016474.5(CCDC174):​c.*605A>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.33 in 152,542 control chromosomes in the GnomAD database, including 8,447 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 0.33 (8436 hom., cov: 33)
  • Exomes 𝑓: 0.25 (11 hom.)
• Consequence: CCDC174 NM_016474.5 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.886

Genes affected

CCDC174 (HGNC:28033): (coiled-coil domain containing 174) The protein encoded by this gene is found in the nucleus, where it interacts with eukaryotic translation initiation factor 4A, isoform 3. The encoded protein appears to be a part of the exon junction complex, which is involved in RNA processing, translation, and nonsense-mediated mRNA decay. A mutation in this gene has been associated with infantile hypotonia with psychomotor retardation. [provided by RefSeq, Mar 2016]

CCDC174 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.379 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CCDC174	NM_016474.5	c.*605A>G		3_prime_UTR_variant	11/11	ENST00000383794.7	NP_057558.3
CCDC174	NM_001410719.1	c.*605A>G		3_prime_UTR_variant	9/9		NP_001397648.1
CCDC174	NR_135523.2	n.1989A>G		non_coding_transcript_exon_variant	10/10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CCDC174	ENST00000383794.7	c.*605A>G		3_prime_UTR_variant	11/11	1	NM_016474.5	ENSP00000373304.3
CCDC174	ENST00000303688.8	c.*605A>G		3_prime_UTR_variant	9/9	5		ENSP00000302344.7

Frequencies

GnomAD3 genomes AF: 0.330 AC: 50184 AN: 152046 Hom.: 8425 Cov.: 33

Gnomad AFR AF: 0.298

Gnomad AMI AF: 0.386

Gnomad AMR AF: 0.387

Gnomad ASJ AF: 0.294

Gnomad EAS AF: 0.245

Gnomad SAS AF: 0.248

Gnomad FIN AF: 0.424

Gnomad MID AF: 0.256

Gnomad NFE AF: 0.335

Gnomad OTH AF: 0.345

GnomAD4 exome AF: 0.246 AC: 93 AN: 378 Hom.: 11 Cov.: 0 AF XY: 0.277 AC XY: 57 AN XY: 206

Gnomad4 AFR exome AF: 0.500

Gnomad4 AMR exome AF: 0.292

Gnomad4 ASJ exome AF: 0.00

Gnomad4 SAS exome AF: 0.167

Gnomad4 FIN exome AF: 0.500

Gnomad4 NFE exome AF: 0.242

Gnomad4 OTH exome AF: 0.208

GnomAD4 genome AF: 0.330 AC: 50230 AN: 152164 Hom.: 8436 Cov.: 33 AF XY: 0.330 AC XY: 24580 AN XY: 74400

Gnomad4 AFR AF: 0.298

Gnomad4 AMR AF: 0.387

Gnomad4 ASJ AF: 0.294

Gnomad4 EAS AF: 0.245

Gnomad4 SAS AF: 0.248

Gnomad4 FIN AF: 0.424

Gnomad4 NFE AF: 0.335

Gnomad4 OTH AF: 0.347

Alfa AF: 0.328 Hom.: 14150

Bravo AF: 0.331

Asia WGS AF: 0.267 AC: 926 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	0.95
DANN	Benign	0.34
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0

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: rs11709673; hg19: chr3-14713306;