rs6877842

Variant names:

• chr5-31532531-G-C
• rs6877842
• NM_018356.3:c.81+58G>C

Variant summary

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

The NM_018356.3(C5orf22):​c.81+58G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.159 in 1,463,870 control chromosomes in the GnomAD database, including 19,342 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 0.16 (2058 hom., cov: 30)
  • Exomes 𝑓: 0.16 (17284 hom.)
• Consequence: C5orf22 NM_018356.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.64
• Publications: 36 publications found

Genes affected

C5orf22 (HGNC:25639): (chromosome 5 open reading frame 22)

DROSHA (HGNC:17904): (drosha ribonuclease III) This gene encodes a ribonuclease (RNase) III double-stranded RNA-specific ribonuclease and subunit of the microprocessor protein complex, which catalyzes the initial processing step of microRNA (miRNA) synthesis. The encoded protein cleaves the stem loop structure from the primary microRNA (pri-miRNA) in the nucleus, yielding the precursor miRNA (pre-miRNA), which is then exported to the cytoplasm for further processing. In a human cell line lacking a functional copy of this gene, canonical miRNA synthesis is reduced. Somatic mutations in this gene have been observed in human patients with kidney cancer. [provided by RefSeq, Sep 2016]

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.181 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_018356.3. 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
	C5orf22	NM_018356.3	MANE Select	c.81+58G>C		intron	N/A	NP_060826.2	Q49AR2-1
	C5orf22	NR_134298.2		n.173+58G>C		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	C5orf22	ENST00000325366.14	TSL:1 MANE Select	c.81+58G>C		intron	N/A	ENSP00000326879.9	Q49AR2-1
	C5orf22	ENST00000510659.5	TSL:1	n.81+58G>C		intron	N/A	ENSP00000423039.1	B4DR92
	DROSHA	ENST00000926013.1		c.-667C>G		5_prime_UTR	Exon 1 of 36	ENSP00000596072.1

Frequencies

GnomAD3 genomes AF: 0.160 AC: 24330 AN: 151718 Hom.: 2057 Cov.: 30

Gnomad AFR AF: 0.184

Gnomad AMI AF: 0.109

Gnomad AMR AF: 0.157

Gnomad ASJ AF: 0.167

Gnomad EAS AF: 0.0233

Gnomad SAS AF: 0.124

Gnomad FIN AF: 0.124

Gnomad MID AF: 0.186

Gnomad NFE AF: 0.166

Gnomad OTH AF: 0.156

GnomAD4 exome AF: 0.159 AC: 208717 AN: 1312034 Hom.: 17284 AF XY: 0.159 AC XY: 103906 AN XY: 655374

African (AFR) AF: 0.188 AC: 5679 AN: 30202

American (AMR) AF: 0.132 AC: 5303 AN: 40236

Ashkenazi Jewish (ASJ) AF: 0.167 AC: 3844 AN: 23082

East Asian (EAS) AF: 0.0181 AC: 700 AN: 38644

South Asian (SAS) AF: 0.124 AC: 9733 AN: 78530

European-Finnish (FIN) AF: 0.129 AC: 6677 AN: 51946

Middle Eastern (MID) AF: 0.166 AC: 885 AN: 5330

European-Non Finnish (NFE) AF: 0.169 AC: 167243 AN: 988976

Other (OTH) AF: 0.157 AC: 8653 AN: 55088

GnomAD4 genome AF: 0.160 AC: 24336 AN: 151836 Hom.: 2058 Cov.: 30 AF XY: 0.158 AC XY: 11701 AN XY: 74178

African (AFR) AF: 0.184 AC: 7634 AN: 41418

American (AMR) AF: 0.156 AC: 2382 AN: 15262

Ashkenazi Jewish (ASJ) AF: 0.167 AC: 579 AN: 3472

East Asian (EAS) AF: 0.0233 AC: 119 AN: 5106

South Asian (SAS) AF: 0.124 AC: 596 AN: 4812

European-Finnish (FIN) AF: 0.124 AC: 1300 AN: 10510

Middle Eastern (MID) AF: 0.190 AC: 55 AN: 290

European-Non Finnish (NFE) AF: 0.165 AC: 11245 AN: 67950

Other (OTH) AF: 0.155 AC: 327 AN: 2104

Alfa AF: 0.156 Hom.: 251

Bravo AF: 0.166

Asia WGS AF: 0.0920 AC: 318 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	6.4
DANN	Benign	0.51
PhyloP100		1.6
PromoterAI		-0.017	Neutral
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: rs6877842; hg19: chr5-31532638; COSMIC: COSV57598375; COSMIC: COSV57598375;