rs623360

Variant names:

• chr1-209779520-C-G
• rs623360
• NM_152485.4:c.*3305G>C

Variant summary

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

The NM_152485.4(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 NM_152485.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.233
• Publications: 11 publications found

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]

ENSG00000289700 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_152485.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	C1orf74	NM_152485.4	MANE Select	c.*3305G>C		3_prime_UTR	Exon 2 of 2	NP_689698.1	Q96LT6
	TRAF3IP3	NM_025228.4	MANE Select	c.1312+146C>G		intron	N/A	NP_079504.2	Q9Y228-1
	TRAF3IP3	NM_001287754.2		c.*117C>G		3_prime_UTR	Exon 7 of 7	NP_001274683.1	B1AJU2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	C1orf74	ENST00000294811.2	TSL:1 MANE Select	c.*3305G>C		3_prime_UTR	Exon 2 of 2	ENSP00000294811.1	Q96LT6
	TRAF3IP3	ENST00000367025.8	TSL:1 MANE Select	c.1312+146C>G		intron	N/A	ENSP00000355992.3	Q9Y228-1
	TRAF3IP3	ENST00000367026.7	TSL:1	c.1252+146C>G		intron	N/A	ENSP00000355993.3	Q9Y228-2

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

African (AFR) AF: 0.208 AC: 3348 AN: 16122

American (AMR) AF: 0.220 AC: 7665 AN: 34874

Ashkenazi Jewish (ASJ) AF: 0.501 AC: 10131 AN: 20202

East Asian (EAS) AF: 0.257 AC: 8294 AN: 32250

South Asian (SAS) AF: 0.371 AC: 23601 AN: 63668

European-Finnish (FIN) AF: 0.368 AC: 18193 AN: 49416

Middle Eastern (MID) AF: 0.476 AC: 1949 AN: 4098

European-Non Finnish (NFE) AF: 0.417 AC: 138947 AN: 333488

Other (OTH) AF: 0.387 AC: 12123 AN: 31358

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

African (AFR) AF: 0.207 AC: 8612 AN: 41512

American (AMR) AF: 0.281 AC: 4294 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.488 AC: 1694 AN: 3468

East Asian (EAS) AF: 0.243 AC: 1260 AN: 5178

South Asian (SAS) AF: 0.352 AC: 1697 AN: 4826

European-Finnish (FIN) AF: 0.381 AC: 4022 AN: 10570

Middle Eastern (MID) AF: 0.418 AC: 122 AN: 292

European-Non Finnish (NFE) AF: 0.419 AC: 28503 AN: 67986

Other (OTH) AF: 0.370 AC: 781 AN: 2108

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 v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.77
CADD	Benign	7.8
DANN	Benign	0.76
PhyloP100		-0.23
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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs623360;

hg19: chr1-209952865;