2-61149328-T-C

Position:

• chr2-61149328-T-C

Variant summary

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

The NM_001143960.3(C2orf74):​c.-122+4132T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.417 in 151,884 control chromosomes in the GnomAD database, including 13,453 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 0.42 (13453 hom., cov: 31)
• Consequence: C2orf74 NM_001143960.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.00300

Genes affected

C2orf74 (HGNC:34439): (chromosome 2 open reading frame 74) Predicted to be integral component of membrane. [provided by Alliance of Genome Resources, Apr 2022]

ENSG00000274769 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.01).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.448 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
C2orf74	NM_001143960.3	c.-122+4132T>C		intron_variant			NP_001137432.1
C2orf74	NM_001316317.2	c.-8+4132T>C		intron_variant			NP_001303246.1
C2orf74	NM_001367069.1	c.-273+4132T>C		intron_variant			NP_001353998.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
C2orf74	ENST00000398622.3	n.-17+4132T>C		intron_variant		1		ENSP00000381621.2
C2orf74	ENST00000426997.5	c.-122+4132T>C		intron_variant		3		ENSP00000398725.1
C2orf74	ENST00000464909.2	c.-8+4132T>C		intron_variant		2		ENSP00000482798.1

Frequencies

GnomAD3 genomes AF: 0.417 AC: 63299 AN: 151766 Hom.: 13429 Cov.: 31

Gnomad AFR AF: 0.453

Gnomad AMI AF: 0.439

Gnomad AMR AF: 0.352

Gnomad ASJ AF: 0.472

Gnomad EAS AF: 0.336

Gnomad SAS AF: 0.250

Gnomad FIN AF: 0.510

Gnomad MID AF: 0.522

Gnomad NFE AF: 0.409

Gnomad OTH AF: 0.446

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

GnomAD4 genome AF: 0.417 AC: 63367 AN: 151884 Hom.: 13453 Cov.: 31 AF XY: 0.418 AC XY: 31046 AN XY: 74214

Gnomad4 AFR AF: 0.453

Gnomad4 AMR AF: 0.353

Gnomad4 ASJ AF: 0.472

Gnomad4 EAS AF: 0.336

Gnomad4 SAS AF: 0.251

Gnomad4 FIN AF: 0.510

Gnomad4 NFE AF: 0.409

Gnomad4 OTH AF: 0.445

Alfa AF: 0.417 Hom.: 20194

Bravo AF: 0.410

Asia WGS AF: 0.280 AC: 975 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	1.8
DANN	Benign	0.36

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs720201; hg19: chr2-61376463;