rs9830735

Variant names:

• chr3-14660128-G-A
• rs9830735
• NM_016474.5:c.307+1199G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_016474.5(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 NM_016474.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.45
• Publications: 4 publications found

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 Gene-Disease associations (from GenCC):

• severe hypotonia-psychomotor developmental delay-strabismus-cardiac septal defect syndrome

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

LOC124906215 (HGNC:):

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 (AMR) allele frequency at 95% confidence interval = 0.379 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CCDC174	NM_016474.5	c.307+1199G>A		intron_variant	Intron 4 of 10	ENST00000383794.7	NP_057558.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CCDC174	ENST00000383794.7	c.307+1199G>A		intron_variant	Intron 4 of 10	1	NM_016474.5	ENSP00000373304.3
CCDC174	ENST00000465759.1	n.371+1199G>A		intron_variant	Intron 4 of 6	1
CCDC174	ENST00000303688.8	c.307+1199G>A		intron_variant	Intron 4 of 8	5		ENSP00000302344.7
CCDC174	ENST00000463438.5	n.380+1199G>A		intron_variant	Intron 4 of 4	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

African (AFR) AF: 0.298 AC: 12350 AN: 41506

American (AMR) AF: 0.387 AC: 5921 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.295 AC: 1023 AN: 3470

East Asian (EAS) AF: 0.246 AC: 1275 AN: 5180

South Asian (SAS) AF: 0.247 AC: 1192 AN: 4826

European-Finnish (FIN) AF: 0.424 AC: 4481 AN: 10576

Middle Eastern (MID) AF: 0.265 AC: 78 AN: 294

European-Non Finnish (NFE) AF: 0.335 AC: 22813 AN: 68006

Other (OTH) AF: 0.347 AC: 734 AN: 2114

Alfa AF: 0.336 Hom.: 1113

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
PhyloP100		-2.5
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: rs9830735; hg19: chr3-14701635;