rs2076153

Positions:

• chr1-209780226-A-G

Variant summary

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

The NM_152485.4(C1orf74):​c.*2599T>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 0.441 in 301,396 control chromosomes in the GnomAD database, including 29,804 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 0.43 (14343 hom., cov: 33)
  • Exomes 𝑓: 0.45 (15461 hom.)
• Consequence: C1orf74 NM_152485.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.251

Genes affected

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

ENSG00000289700 (HGNC:):

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=-0.85).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.535 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
C1orf74	NM_152485.4	c.*2599T>C		3_prime_UTR_variant	2/2	ENST00000294811.2	NP_689698.1
TRAF3IP3	NM_025228.4	c.1313-244A>G		intron_variant		ENST00000367025.8	NP_079504.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
C1orf74	ENST00000294811	c.*2599T>C		3_prime_UTR_variant	2/2	1	NM_152485.4	ENSP00000294811.1
ENSG00000289700	ENST00000696133	c.*3423T>C		3_prime_UTR_variant	10/10			ENSP00000512426.1
TRAF3IP3	ENST00000367025.8	c.1313-244A>G		intron_variant		1	NM_025228.4	ENSP00000355992.3

Frequencies

GnomAD3 genomes AF: 0.432 AC: 65596 AN: 151964 Hom.: 14330 Cov.: 33

Gnomad AFR AF: 0.397

Gnomad AMI AF: 0.415

Gnomad AMR AF: 0.485

Gnomad ASJ AF: 0.511

Gnomad EAS AF: 0.551

Gnomad SAS AF: 0.439

Gnomad FIN AF: 0.392

Gnomad MID AF: 0.430

Gnomad NFE AF: 0.433

Gnomad OTH AF: 0.444

GnomAD4 exome AF: 0.450 AC: 67160 AN: 149314 Hom.: 15461 Cov.: 3 AF XY: 0.449 AC XY: 34593 AN XY: 76974

Gnomad4 AFR exome AF: 0.401

Gnomad4 AMR exome AF: 0.482

Gnomad4 ASJ exome AF: 0.528

Gnomad4 EAS exome AF: 0.613

Gnomad4 SAS exome AF: 0.464

Gnomad4 FIN exome AF: 0.373

Gnomad4 NFE exome AF: 0.432

Gnomad4 OTH exome AF: 0.451

GnomAD4 genome AF: 0.432 AC: 65642 AN: 152082 Hom.: 14343 Cov.: 33 AF XY: 0.431 AC XY: 32067 AN XY: 74352

Gnomad4 AFR AF: 0.396

Gnomad4 AMR AF: 0.485

Gnomad4 ASJ AF: 0.511

Gnomad4 EAS AF: 0.552

Gnomad4 SAS AF: 0.438

Gnomad4 FIN AF: 0.392

Gnomad4 NFE AF: 0.433

Gnomad4 OTH AF: 0.446

Alfa AF: 0.440 Hom.: 14018

Bravo AF: 0.434

Asia WGS AF: 0.475 AC: 1652 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	6.9
DANN	Benign	0.75

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: rs2076153; hg19: chr1-209953571;