rs7217038

Variant names:

• chr17-2748083-T-A
• rs7217038
• NM_001355573.2:c.-24+1328A>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BS1 BS2

The NM_001355573.2(CCDC92B):​c.-24+1328A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00517 in 526,976 control chromosomes in the GnomAD database, including 62 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 0.014 (50 hom., cov: 32)
  • Exomes 𝑓: 0.0017 (12 hom.)
• Consequence: CCDC92B NM_001355573.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.401
• Publications: 4 publications found

Genes affected

CCDC92B (HGNC:52279): (coiled-coil domain containing 92B)

MIR1253 (HGNC:35318): (microRNA 1253) 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]

hsa-mir-1253 (HGNC:):

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BS1: Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.0137 (2090/152240) while in subpopulation AFR AF = 0.0473 (1963/41536). AF 95% confidence interval is 0.0455. There are 50 homozygotes in GnomAd4. There are 927 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 50 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CCDC92B	NM_001355573.2	c.-24+1328A>T		intron_variant	Intron 1 of 3	ENST00000614400.2	NP_001342502.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CCDC92B	ENST00000614400.2	c.-24+1328A>T		intron_variant	Intron 1 of 3	6	NM_001355573.2	ENSP00000509343.1
MIR1253	ENST00000408273.1	n.100A>T		non_coding_transcript_exon_variant	Exon 1 of 1	6
hsa-mir-1253	ENST00000609567.1	n.6T>A		non_coding_transcript_exon_variant	Exon 1 of 1	6

Frequencies

GnomAD3 genomes AF: 0.0137 AC: 2087 AN: 152122 Hom.: 50 Cov.: 32

Gnomad AFR AF: 0.0473

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00622

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000162

Gnomad OTH AF: 0.0100

GnomAD2 exomes AF: 0.00356 AC: 857 AN: 240580 AF XY: 0.00275

Gnomad AFR exome AF: 0.0484

Gnomad AMR exome AF: 0.00287

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000820

Gnomad OTH exome AF: 0.000838

GnomAD4 exome AF: 0.00169 AC: 632 AN: 374736 Hom.: 12 Cov.: 0 AF XY: 0.00138 AC XY: 295 AN XY: 214166

African (AFR) AF: 0.0454 AC: 470 AN: 10346

American (AMR) AF: 0.00293 AC: 105 AN: 35882

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 11678

East Asian (EAS) AF: 0.00 AC: 0 AN: 13158

South Asian (SAS) AF: 0.0000601 AC: 4 AN: 66606

European-Finnish (FIN) AF: 0.0000380 AC: 1 AN: 26314

Middle Eastern (MID) AF: 0.00181 AC: 5 AN: 2758

European-Non Finnish (NFE) AF: 0.0000784 AC: 15 AN: 191424

Other (OTH) AF: 0.00193 AC: 32 AN: 16570

GnomAD4 genome AF: 0.0137 AC: 2090 AN: 152240 Hom.: 50 Cov.: 32 AF XY: 0.0125 AC XY: 927 AN XY: 74434

African (AFR) AF: 0.0473 AC: 1963 AN: 41536

American (AMR) AF: 0.00621 AC: 95 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5168

South Asian (SAS) AF: 0.00 AC: 0 AN: 4830

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10614

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.000162 AC: 11 AN: 68012

Other (OTH) AF: 0.00994 AC: 21 AN: 2112

Alfa AF: 0.00653 Hom.: 7

Bravo AF: 0.0160

Asia WGS AF: 0.00260 AC: 9 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	4.2
DANN	Benign	0.72
PhyloP100		-0.40

Splicing

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

Other links and lift over

dbSNP: rs7217038; hg19: chr17-2651377;