rs9830735

Positions:

• chr3-14660128-G-A

Variant summary

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

The ENST00000383794.7(CCDC174):​c.307+1199G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.33 in 152,182 control chromosomes in the GnomAD database, including 8,438 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 (8438 hom., cov: 33)
• Consequence: CCDC174 ENST00000383794.7 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.45

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]

LOC124906215 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• 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.307+1199G>A		intron_variant		ENST00000383794.7	NP_057558.3
LOC124906215	XR_007095827.1	n.427-938C>T		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CCDC174	ENST00000383794.7	c.307+1199G>A		intron_variant		1	NM_016474.5	ENSP00000373304	P1
CCDC174	ENST00000465759.1	n.371+1199G>A		intron_variant, non_coding_transcript_variant		1
CCDC174	ENST00000303688.8	c.307+1199G>A		intron_variant		5		ENSP00000302344
CCDC174	ENST00000463438.5	n.380+1199G>A		intron_variant, non_coding_transcript_variant		2

Frequencies

GnomAD3 genomes AF: 0.330 AC: 50179 AN: 152064 Hom.: 8428 Cov.: 33

Gnomad AFR AF: 0.298

Gnomad AMI AF: 0.387

Gnomad AMR AF: 0.386

Gnomad ASJ AF: 0.295

Gnomad EAS AF: 0.246

Gnomad SAS AF: 0.248

Gnomad FIN AF: 0.424

Gnomad MID AF: 0.256

Gnomad NFE AF: 0.335

Gnomad OTH AF: 0.346

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.330 AC: 50219 AN: 152182 Hom.: 8438 Cov.: 33 AF XY: 0.330 AC XY: 24579 AN XY: 74396

Gnomad4 AFR AF: 0.298

Gnomad4 AMR AF: 0.387

Gnomad4 ASJ AF: 0.295

Gnomad4 EAS AF: 0.246

Gnomad4 SAS AF: 0.247

Gnomad4 FIN AF: 0.424

Gnomad4 NFE AF: 0.335

Gnomad4 OTH AF: 0.347

Alfa AF: 0.338 Hom.: 1075

Bravo AF: 0.331

Asia WGS AF: 0.264 AC: 914 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	0.23
DANN	Benign	0.69

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: rs9830735; hg19: chr3-14701635;