3-14655811-A-G

Position:

• chr3-14655811-A-G

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_016474.5(CCDC174):​c.248+182A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.436 in 152,070 control chromosomes in the GnomAD database, including 16,469 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.44 (16469 hom., cov: 32)
• Consequence: CCDC174 NM_016474.5 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.310

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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BP6: Variant 3-14655811-A-G is Benign according to our data. Variant chr3-14655811-A-G is described in ClinVar as [Benign]. Clinvar id is 1253287.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.636 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CCDC174	NM_016474.5	c.248+182A>G		intron_variant		ENST00000383794.7	NP_057558.3
CCDC174	NM_001410719.1	c.248+182A>G		intron_variant			NP_001397648.1
CCDC174	XM_017006555.3	c.248+182A>G		intron_variant			XP_016862044.1
CCDC174	NR_135523.2	n.323+182A>G		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CCDC174	ENST00000383794.7	c.248+182A>G		intron_variant		1	NM_016474.5	ENSP00000373304	P1
CCDC174	ENST00000465759.1	n.312+182A>G		intron_variant, non_coding_transcript_variant		1
CCDC174	ENST00000303688.8	c.248+182A>G		intron_variant		5		ENSP00000302344
CCDC174	ENST00000463438.5	n.321+182A>G		intron_variant, non_coding_transcript_variant		2

Frequencies

GnomAD3 genomes AF: 0.437 AC: 66366 AN: 151952 Hom.: 16474 Cov.: 32

Gnomad AFR AF: 0.194

Gnomad AMI AF: 0.434

Gnomad AMR AF: 0.407

Gnomad ASJ AF: 0.586

Gnomad EAS AF: 0.472

Gnomad SAS AF: 0.654

Gnomad FIN AF: 0.440

Gnomad MID AF: 0.561

Gnomad NFE AF: 0.563

Gnomad OTH AF: 0.466

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

GnomAD4 genome AF: 0.436 AC: 66375 AN: 152070 Hom.: 16469 Cov.: 32 AF XY: 0.435 AC XY: 32380 AN XY: 74356

Gnomad4 AFR AF: 0.194

Gnomad4 AMR AF: 0.407

Gnomad4 ASJ AF: 0.586

Gnomad4 EAS AF: 0.471

Gnomad4 SAS AF: 0.655

Gnomad4 FIN AF: 0.440

Gnomad4 NFE AF: 0.563

Gnomad4 OTH AF: 0.464

Alfa AF: 0.361 Hom.: 1074

Bravo AF: 0.419

Asia WGS AF: 0.536 AC: 1866 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

May 10, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	4.5
DANN	Benign	0.80

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: rs13090327; hg19: chr3-14697318;