rs6997249

Variant names:

• chr8-129484119-G-A
• rs6997249
• ENST00000446592.7:n.313-3429C>T

Variant summary

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

The ENST00000446592.7(CCDC26):​n.313-3429C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.277 in 154,620 control chromosomes in the GnomAD database, including 6,402 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 0.28 (6295 hom., cov: 32)
  • Exomes 𝑓: 0.28 (107 hom.)
• Consequence: CCDC26 ENST00000446592.7 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.03
• Publications: 11 publications found

Genes affected

CCDC26 (HGNC:28416): (CCDC26 long non-coding RNA)

MIR3686 (HGNC:38887): (microRNA 3686) microRNAs (miRNAs) are short (20-24 nt) non-coding RNAs that are involved in post-transcriptional regulation of gene expression in multicellular organisms by affecting both the stability and translation of mRNAs. miRNAs are transcribed by RNA polymerase II as part of capped and polyadenylated primary transcripts (pri-miRNAs) that can be either protein-coding or non-coding. The primary transcript is cleaved by the Drosha ribonuclease III enzyme to produce an approximately 70-nt stem-loop precursor miRNA (pre-miRNA), which is further cleaved by the cytoplasmic Dicer ribonuclease to generate the mature miRNA and antisense miRNA star (miRNA*) products. The mature miRNA is incorporated into a RNA-induced silencing complex (RISC), which recognizes target mRNAs through imperfect base pairing with the miRNA and most commonly results in translational inhibition or destabilization of the target mRNA. The RefSeq represents the predicted microRNA stem-loop. [provided by RefSeq, Sep 2009]

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.316 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000446592.7. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MIR3686	NR_037457.1		n.24C>T		non_coding_transcript_exon	Exon 1 of 1
	CCDC26	NR_130917.1		n.313-3429C>T		intron	N/A
	CCDC26	NR_130918.1		n.137+90763C>T		intron	N/A

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CCDC26	ENST00000446592.7	TSL:1	n.313-3429C>T		intron	N/A
	CCDC26	ENST00000523151.6	TSL:1	n.135+90763C>T		intron	N/A
	MIR3686	ENST00000577904.1	TSL:6	n.24C>T		non_coding_transcript_exon	Exon 1 of 1

Frequencies

GnomAD3 genomes AF: 0.277 AC: 42090 AN: 151980 Hom.: 6293 Cov.: 32

Gnomad AFR AF: 0.209

Gnomad AMI AF: 0.268

Gnomad AMR AF: 0.275

Gnomad ASJ AF: 0.241

Gnomad EAS AF: 0.126

Gnomad SAS AF: 0.174

Gnomad FIN AF: 0.407

Gnomad MID AF: 0.222

Gnomad NFE AF: 0.320

Gnomad OTH AF: 0.269

GnomAD2 exomes AF: 0.298 AC: 1583 AN: 5318 AF XY: 0.315

Gnomad AFR exome AF: 0.217

Gnomad AMR exome AF: 0.264

Gnomad ASJ exome AF: 0.327

Gnomad EAS exome AF: 0.0469

Gnomad NFE exome AF: 0.312

Gnomad OTH exome AF: 0.218

GnomAD4 exome AF: 0.280 AC: 707 AN: 2522 Hom.: 107 Cov.: 0 AF XY: 0.298 AC XY: 391 AN XY: 1310

African (AFR) AF: 0.237 AC: 18 AN: 76

American (AMR) AF: 0.125 AC: 1 AN: 8

Ashkenazi Jewish (ASJ) AF: 0.500 AC: 2 AN: 4

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AF: 0.208 AC: 20 AN: 96

European-Finnish (FIN) AF: 0.400 AC: 171 AN: 428

Middle Eastern (MID) AF: 0.257 AC: 402 AN: 1564

European-Non Finnish (NFE) AF: 0.287 AC: 47 AN: 164

Other (OTH) AF: 0.253 AC: 46 AN: 182

GnomAD4 genome AF: 0.277 AC: 42103 AN: 152098 Hom.: 6295 Cov.: 32 AF XY: 0.279 AC XY: 20775 AN XY: 74354

African (AFR) AF: 0.209 AC: 8667 AN: 41498

American (AMR) AF: 0.275 AC: 4195 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.241 AC: 835 AN: 3470

East Asian (EAS) AF: 0.126 AC: 650 AN: 5176

South Asian (SAS) AF: 0.174 AC: 841 AN: 4826

European-Finnish (FIN) AF: 0.407 AC: 4294 AN: 10556

Middle Eastern (MID) AF: 0.228 AC: 67 AN: 294

European-Non Finnish (NFE) AF: 0.320 AC: 21743 AN: 67970

Other (OTH) AF: 0.268 AC: 567 AN: 2114

Alfa AF: 0.317 Hom.: 988

Bravo AF: 0.266

Asia WGS AF: 0.149 AC: 518 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	4.8
DANN	Benign	0.73
PhyloP100		1.0

Splicing

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

Other links and lift over

dbSNP: rs6997249; hg19: chr8-130496365;