rs7217038

Variant names:

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

Variant summary

Our verdict is Benign. Variant got -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

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

Verdict is Benign. Variant got -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 male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
• 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

GnomAD3 exomes AF: 0.00356 AC: 857 AN: 240580 Hom.: 26 AF XY: 0.00275 AC XY: 362 AN XY: 131564

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 SAS exome AF: 0.0000329

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

Gnomad4 AFR exome AF: 0.0454

Gnomad4 AMR exome AF: 0.00293

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000601

Gnomad4 FIN exome AF: 0.0000380

Gnomad4 NFE exome AF: 0.0000784

Gnomad4 OTH exome AF: 0.00193

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

Gnomad4 AFR AF: 0.0473

Gnomad4 AMR AF: 0.00621

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000162

Gnomad4 OTH AF: 0.00994

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

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs7217038; hg19: chr17-2651377;