7-1022730-T-C

Variant names:

• chr7-1022730-T-C
• rs1057558
• NM_001318252.2:c.130-12587A>G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001318252.2(C7orf50):​c.130-12587A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.196 in 152,066 control chromosomes in the GnomAD database, including 3,116 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 0.20 (3116 hom., cov: 33)
• Consequence: C7orf50 NM_001318252.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.852

Genes affected

C7orf50 (HGNC:22421): (chromosome 7 open reading frame 50) Enables RNA binding activity. [provided by Alliance of Genome Resources, Apr 2022]

MIR339 (HGNC:31776): (microRNA 339) 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

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.231 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
C7orf50	NM_001318252.2	c.130-12587A>G		intron_variant	Intron 2 of 4	ENST00000397098.8	NP_001305181.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
C7orf50	ENST00000397098.8	c.130-12587A>G		intron_variant	Intron 2 of 4	1	NM_001318252.2	ENSP00000380286.3

Frequencies

GnomAD3 genomes AF: 0.196 AC: 29819 AN: 151948 Hom.: 3112 Cov.: 33

Gnomad AFR AF: 0.161

Gnomad AMI AF: 0.176

Gnomad AMR AF: 0.237

Gnomad ASJ AF: 0.141

Gnomad EAS AF: 0.132

Gnomad SAS AF: 0.148

Gnomad FIN AF: 0.265

Gnomad MID AF: 0.136

Gnomad NFE AF: 0.210

Gnomad OTH AF: 0.197

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

GnomAD4 genome AF: 0.196 AC: 29838 AN: 152066 Hom.: 3116 Cov.: 33 AF XY: 0.197 AC XY: 14617 AN XY: 74334

Gnomad4 AFR AF: 0.161

Gnomad4 AMR AF: 0.237

Gnomad4 ASJ AF: 0.141

Gnomad4 EAS AF: 0.132

Gnomad4 SAS AF: 0.148

Gnomad4 FIN AF: 0.265

Gnomad4 NFE AF: 0.210

Gnomad4 OTH AF: 0.194

Alfa AF: 0.186 Hom.: 1403

Bravo AF: 0.193

Asia WGS AF: 0.136 AC: 472 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.91
DANN	Benign	0.62

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

Publications

LitVar

Other links and lift over

dbSNP: rs1057558; hg19: chr7-1062366;