NM_032137.5:c.2496-1456G>A

Variant names:

• chr3-14770611-G-A
• rs7651825
• NM_032137.5:c.2496-1456G>A

Variant summary

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

The NM_032137.5(C3orf20):​c.2496-1456G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.316 in 151,854 control chromosomes in the GnomAD database, including 9,200 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 0.32 (9200 hom., cov: 31)
• Consequence: C3orf20 NM_032137.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.123
• Publications: 4 publications found

Genes affected

C3orf20 (HGNC:25320): (chromosome 3 open reading frame 20) Located in cytoplasm. [provided by Alliance of Genome Resources, Apr 2022]

C3orf20 Gene-Disease associations (from GenCC):

• neuromyelitis optica

  Inheritance: AD Classification: LIMITED Submitted by: Ambry Genetics

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.433 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
C3orf20	NM_032137.5	c.2496-1456G>A		intron_variant	Intron 15 of 16	ENST00000253697.8	NP_115513.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
C3orf20	ENST00000253697.8	c.2496-1456G>A		intron_variant	Intron 15 of 16	1	NM_032137.5	ENSP00000253697.3
C3orf20	ENST00000412910.1	c.2130-1456G>A		intron_variant	Intron 15 of 16	1		ENSP00000396081.1
C3orf20	ENST00000435614.5	c.2130-1456G>A		intron_variant	Intron 15 of 16	1		ENSP00000402933.1

Frequencies

GnomAD3 genomes AF: 0.316 AC: 47993 AN: 151736 Hom.: 9203 Cov.: 31

Gnomad AFR AF: 0.106

Gnomad AMI AF: 0.334

Gnomad AMR AF: 0.342

Gnomad ASJ AF: 0.397

Gnomad EAS AF: 0.227

Gnomad SAS AF: 0.168

Gnomad FIN AF: 0.402

Gnomad MID AF: 0.351

Gnomad NFE AF: 0.437

Gnomad OTH AF: 0.354

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

GnomAD4 genome AF: 0.316 AC: 47998 AN: 151854 Hom.: 9200 Cov.: 31 AF XY: 0.310 AC XY: 22969 AN XY: 74166

African (AFR) AF: 0.106 AC: 4379 AN: 41442

American (AMR) AF: 0.341 AC: 5212 AN: 15264

Ashkenazi Jewish (ASJ) AF: 0.397 AC: 1378 AN: 3472

East Asian (EAS) AF: 0.227 AC: 1172 AN: 5152

South Asian (SAS) AF: 0.167 AC: 805 AN: 4812

European-Finnish (FIN) AF: 0.402 AC: 4229 AN: 10518

Middle Eastern (MID) AF: 0.361 AC: 106 AN: 294

European-Non Finnish (NFE) AF: 0.437 AC: 29670 AN: 67888

Other (OTH) AF: 0.353 AC: 743 AN: 2102

Alfa AF: 0.395 Hom.: 41639

Bravo AF: 0.310

Asia WGS AF: 0.186 AC: 649 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	0.83
DANN	Benign	0.77
PhyloP100		-0.12
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

Other links and lift over

dbSNP: rs7651825; hg19: chr3-14812118; COSMIC: COSV53786001; COSMIC: COSV53786001;