chr2-61149328-T-C

Variant names:

• chr2-61149328-T-C
• rs720201
• ENST00000398622.3:n.-17+4132T>C

Variant summary

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

The ENST00000398622.3(C2orf74):​n.-17+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 ENST00000398622.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.00300
• Publications: 26 publications found

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:):

C2orf74-AS1 (HGNC:56377): (C2orf74 antisense RNA 1)

ACMG classification

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
C2orf74	NM_001143960.3	c.-122+4132T>C		intron_variant	Intron 1 of 3		NP_001137432.1
C2orf74	NM_001316317.2	c.-8+4132T>C		intron_variant	Intron 1 of 2		NP_001303246.1
C2orf74	NM_001367069.1	c.-273+4132T>C		intron_variant	Intron 1 of 4		NP_001353998.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
C2orf74	ENST00000398622.3	n.-17+4132T>C		intron_variant	Intron 1 of 4	1		ENSP00000381621.2
C2orf74	ENST00000426997.5	c.-122+4132T>C		intron_variant	Intron 1 of 3	3		ENSP00000398725.1
C2orf74	ENST00000464909.2	c.-8+4132T>C		intron_variant	Intron 1 of 2	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

African (AFR) AF: 0.453 AC: 18779 AN: 41424

American (AMR) AF: 0.353 AC: 5367 AN: 15224

Ashkenazi Jewish (ASJ) AF: 0.472 AC: 1637 AN: 3470

East Asian (EAS) AF: 0.336 AC: 1733 AN: 5158

South Asian (SAS) AF: 0.251 AC: 1210 AN: 4824

European-Finnish (FIN) AF: 0.510 AC: 5373 AN: 10536

Middle Eastern (MID) AF: 0.500 AC: 146 AN: 292

European-Non Finnish (NFE) AF: 0.409 AC: 27783 AN: 67934

Other (OTH) AF: 0.445 AC: 940 AN: 2114

Alfa AF: 0.415 Hom.: 28845

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
PhyloP100		-0.0030
Mutation Taster		=100/0	polymorphism (auto)

Splicing

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

Other links and lift over

dbSNP: rs720201; hg19: chr2-61376463;