rs6776417

chr3-14657507-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.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

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]

ACMG classification

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CCDC174	NM_016474.5	c.249-1364A>G		intron_variant		ENST00000383794.7
CCDC174	NM_001410719.1	c.249-1364A>G		intron_variant
CCDC174	XM_017006555.3	c.249-1364A>G		intron_variant
CCDC174	NR_135523.2	n.324-1364A>G		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CCDC174	ENST00000383794.7	c.249-1364A>G		intron_variant		1	NM_016474.5	P1
CCDC174	ENST00000465759.1	n.313-1364A>G		intron_variant, non_coding_transcript_variant		1
CCDC174	ENST00000303688.8	c.249-1364A>G		intron_variant		5
CCDC174	ENST00000463438.5	n.322-1364A>G		intron_variant, non_coding_transcript_variant		2

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

Gnomad4 AFR AF: 0.298

Gnomad4 AMR AF: 0.387

Gnomad4 ASJ AF: 0.295

Gnomad4 EAS AF: 0.247

Gnomad4 SAS AF: 0.247

Gnomad4 FIN AF: 0.423

Gnomad4 NFE AF: 0.336

Gnomad4 OTH AF: 0.348

Alfa AF: 0.338 Hom.: 1076

Bravo AF: 0.331

Asia WGS AF: 0.267 AC: 925 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
Cadd	Benign	5.5
Dann	Benign	0.68

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: rs6776417; hg19: chr3-14699014;