rs623360

Positions:

• chr1-209779520-C-G

Variant summary

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

The ENST00000294811.2(C1orf74):​c.*3305G>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.374 in 737,612 control chromosomes in the GnomAD database, including 54,061 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 0.34 (9480 hom., cov: 33)
  • Exomes 𝑓: 0.38 (44581 hom.)
• Consequence: C1orf74 ENST00000294811.2 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.233

Genes affected

C1orf74 (HGNC:26319): (chromosome 1 open reading frame 74)

TRAF3IP3 (HGNC:30766): (TRAF3 interacting protein 3) The gene encodes a protein that mediates cell growth by modulating the c-Jun N-terminal kinase signal transduction pathway. The encoded protein may also interact with a large multi-protein assembly containing the phosphatase 2A catalytic subunit. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Dec 2013]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.77).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.415 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
C1orf74	NM_152485.4	c.*3305G>C		3_prime_UTR_variant	2/2	ENST00000294811.2	NP_689698.1
TRAF3IP3	NM_025228.4	c.1312+146C>G		intron_variant		ENST00000367025.8	NP_079504.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
C1orf74	ENST00000294811.2	c.*3305G>C		3_prime_UTR_variant	2/2	1	NM_152485.4	ENSP00000294811	P1
TRAF3IP3	ENST00000367025.8	c.1312+146C>G		intron_variant		1	NM_025228.4	ENSP00000355992	P1

Frequencies

GnomAD3 genomes AF: 0.338 AC: 51313 AN: 152018 Hom.: 9476 Cov.: 33

Gnomad AFR AF: 0.207

Gnomad AMI AF: 0.384

Gnomad AMR AF: 0.282

Gnomad ASJ AF: 0.488

Gnomad EAS AF: 0.242

Gnomad SAS AF: 0.352

Gnomad FIN AF: 0.381

Gnomad MID AF: 0.420

Gnomad NFE AF: 0.419

Gnomad OTH AF: 0.369

GnomAD4 exome AF: 0.383 AC: 224251 AN: 585476 Hom.: 44581 Cov.: 6 AF XY: 0.387 AC XY: 121938 AN XY: 315458

Gnomad4 AFR exome AF: 0.208

Gnomad4 AMR exome AF: 0.220

Gnomad4 ASJ exome AF: 0.501

Gnomad4 EAS exome AF: 0.257

Gnomad4 SAS exome AF: 0.371

Gnomad4 FIN exome AF: 0.368

Gnomad4 NFE exome AF: 0.417

Gnomad4 OTH exome AF: 0.387

GnomAD4 genome AF: 0.337 AC: 51335 AN: 152136 Hom.: 9480 Cov.: 33 AF XY: 0.335 AC XY: 24894 AN XY: 74380

Gnomad4 AFR AF: 0.207

Gnomad4 AMR AF: 0.281

Gnomad4 ASJ AF: 0.488

Gnomad4 EAS AF: 0.243

Gnomad4 SAS AF: 0.352

Gnomad4 FIN AF: 0.381

Gnomad4 NFE AF: 0.419

Gnomad4 OTH AF: 0.370

Alfa AF: 0.379 Hom.: 1422

Bravo AF: 0.321

Asia WGS AF: 0.315 AC: 1094 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.77
CADD	Benign	7.8
DANN	Benign	0.76

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: rs623360; hg19: chr1-209952865;