rs6776417

Variant names:

• chr3-14657507-A-G
• rs6776417
• NM_016474.5:c.249-1364A>G

Variant summary

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

The NM_016474.5(CCDC174):​c.249-1364A>G 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 152,138 control chromosomes in the GnomAD database, including 8,454 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 (8454 hom., cov: 32)
• Consequence: CCDC174 NM_016474.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.432
• Publications: 3 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

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.379 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_016474.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CCDC174	NM_016474.5	MANE Select	c.249-1364A>G		intron	N/A	NP_057558.3
	CCDC174	NM_001410719.1		c.249-1364A>G		intron	N/A	NP_001397648.1
	CCDC174	NR_135523.2		n.324-1364A>G		intron	N/A

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CCDC174	ENST00000383794.7	TSL:1 MANE Select	c.249-1364A>G		intron	N/A	ENSP00000373304.3
	CCDC174	ENST00000465759.1	TSL:1	n.313-1364A>G		intron	N/A
	CCDC174	ENST00000303688.8	TSL:5	c.249-1364A>G		intron	N/A	ENSP00000302344.7

Frequencies

GnomAD3 genomes AF: 0.330 AC: 50205 AN: 152020 Hom.: 8443 Cov.: 32

Gnomad AFR AF: 0.298

Gnomad AMI AF: 0.385

Gnomad AMR AF: 0.387

Gnomad ASJ AF: 0.295

Gnomad EAS AF: 0.247

Gnomad SAS AF: 0.248

Gnomad FIN AF: 0.423

Gnomad MID AF: 0.256

Gnomad NFE AF: 0.336

Gnomad OTH AF: 0.345

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

GnomAD4 genome AF: 0.330 AC: 50250 AN: 152138 Hom.: 8454 Cov.: 32 AF XY: 0.331 AC XY: 24585 AN XY: 74384

African (AFR) AF: 0.298 AC: 12359 AN: 41476

American (AMR) AF: 0.387 AC: 5923 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.295 AC: 1024 AN: 3470

East Asian (EAS) AF: 0.247 AC: 1280 AN: 5184

South Asian (SAS) AF: 0.247 AC: 1192 AN: 4828

European-Finnish (FIN) AF: 0.423 AC: 4473 AN: 10572

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

European-Non Finnish (NFE) AF: 0.336 AC: 22837 AN: 68000

Other (OTH) AF: 0.348 AC: 734 AN: 2112

Alfa AF: 0.336 Hom.: 1112

Bravo AF: 0.331

Asia WGS AF: 0.267 AC: 925 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	5.5
DANN	Benign	0.68
PhyloP100		0.43
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: rs6776417; hg19: chr3-14699014;